Working Together to End Cancer as We Know It

November 03, 2021

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Yale Cancer Center Grand Rounds | November 2, 2021

Presented by: Dr. Norman 'Ned' Sharpless

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00:00OK, why don't we get started?
00:02We have a pretty full agenda
00:04and and people will join love.
00:06Thank you all for coming.
00:07I'm Roy herbst.
00:08Cue from medical oncology and
00:10of all the jobs I do here.
00:12I think my greatest honor is to
00:15organize the Calabrese lecture each
00:17year and you'll hear why the Paul
00:19Calabrese was a mentor and friend to me.
00:21And it's great to have his family together.
00:23I just wish we could have all
00:25been together here in person,
00:26but it's great to be here.
00:28You know, virtually and to have.
00:31A discussion you know at the 50th
00:33anniversary of the National Cancer Act,
00:35and as you'll see,
00:36Yale had so much to do with it.
00:38Paul, Vince,
00:39and we're gonna hear from
00:40the NCI director as we start.
00:42I'm gonna turn it over to
00:43our current interim director.
00:44You know who je to make a
00:46few welcoming remarks?
00:47Anita,
00:48thank you Roy.
00:49And good afternoon everybody.
00:51Welcome to Cancer Center,
00:52grand rounds and I want to
00:54thank the Calabrese family
00:55for joining us today and
00:58also that we look forward to having
00:59you back here in person hopefully
01:01soon. In New Haven in and share this day
01:05with you want to especially thank Doctor
01:07Sharpless for taking time out of his busy
01:09schedule to present this
01:10year's annual lectureship and
01:13share his insights on the National Cancer
01:15Institute priorities and reflections.
01:17As we also celebrate
01:1850 years of the National Cancer Act
01:20and Roy, thank you always for all your
01:23thoughtful leadership of the annual
01:25Calabrisi Lectureship, which gives us an
01:27opportunity to pause and remember
01:29the impact of one of the
01:30great leaders and influencers
01:31in Cancer Research.
01:33In care and with that. Roy
01:35please, I'm going
01:36to hand it back to you.
01:37Thanks, you know, Renee,
01:38if you could put up that first
01:39slide I I'm going to introduce Vince
01:41Devita now and I just will start.
01:42I just want to show one slide
01:44that I think says it all.
01:46So you know you know.
01:48So there you see events that that picture
01:51is probably right outside of Ned's office.
01:53I think you probably passed it on his
01:55way today and Vince can tell us if he wants.
01:59That represents and then we.
02:00Of course, you see Vince with a
02:02former president and I always ask you,
02:03Vince, what?
02:03What did he tell you that made you
02:05laugh but will take the slide down?
02:06And I'd like Vince to give us just
02:08a couple minutes perspective given
02:10that he was there when it happened.
02:12Yeah, well actually
02:14it was. I said something
02:14to him that made him laugh.
02:16He was not easy to make laugh and
02:19people always ask him what was it.
02:20You said I haven't the
02:22foggiest notion what I said,
02:23but whatever it was,
02:25it seemed to be funny.
02:26Riots would say two things
02:28about the early days of the NCI.
02:30I had sort of an advance look at
02:32the Cancer Act because I was taking
02:35care of the the guy who wrote
02:37it at the time and so he gave me
02:40insights into what was going on.
02:41I like most people in my age.
02:43I didn't care for the idea,
02:45but I grew to like it as as time went
02:47on and I became director of the Institute.
02:49I like to remind people that the mandate
02:52of the Cancer Act was to support research.
02:55The application of the results of
02:56research to reduce the incidence,
02:58morbidity and mortality from cancer.
03:01So that was on our mind as we
03:02started to spend the money and we
03:04did pretty well in the first decade.
03:0685% of the money went into basic
03:10research and we had two problems.
03:12I think Med would like to have.
03:13Now there were problems for us.
03:15We couldn't spend all the money.
03:17It's very hard when you weren't
03:19staffed up to spend.
03:20$100 million and you have to keep
03:22in mind that the NIH doesn't have
03:24what we call no year money.
03:26You get money allocated in a given.
03:28You have to spend it,
03:29but you have to give it back.
03:30Giving it back was politically untenable,
03:33so we had to figure out how to
03:35spend it resorted to contracts,
03:37because we could do that faster,
03:39which is a very controversial decision.
03:42The other the other problem we
03:43had was the grant paylines.
03:44They were consistently around 50%,
03:47but we were funding 50% of approved.
03:49Applications and there were people
03:51who said my goodness that's higher
03:53than we've ever seen.
03:55It turns out, of course,
03:5650% essentially approving 100% of all
03:59grants that had a fundable paceline.
04:02Most grants are are not rejected,
04:04it just given a score that you wouldn't fund.
04:06So when you fund all 50% of
04:09approved application,
04:10and every grant up to score 250
04:12so it was funded in those days,
04:14so that those are the House here
04:16on days for submitting a grant.
04:18We also did the same thing.
04:20Any applications that we,
04:21the clinical trials program,
04:23went from $9 million to $110
04:26million in six years,
04:28and the cancer centers went from 3 to 15,
04:31so that that was the application side.
04:32The application side was controversial.
04:35The NIH novice,
04:36or itself as applying research and
04:38the Cancer Act changed all that.
04:41How have we done?
04:42Well,
04:43you know we decreased.
04:44Incidents began to decrease in
04:461990 and morbidity has been fat,
04:48vastly diminished in both surgery,
04:52radiation therapy and systemic therapies,
04:54and mortality has been coming
04:56down steadily since 1991,
04:58so the mandate I think
05:00has been followed over a time period that was
05:03perhaps longer than most people anticipated.
05:05I think it's fitting to celebrate the
05:0750th anniversary at the Calibri Selectah,
05:09though, because Paul was very heavily
05:11invested in the in the war on cancer.
05:14And he served as advisers to two presidents.
05:16It was appointed the chairman of the
05:20National Cancer Advisory Board by one
05:23president and the President and a member
05:25of the President's Cancer Panel by another.
05:28Both presidents were different and
05:30they were from different parties,
05:32emphasizing polls. Diplomatic skills.
05:34When I came to Yale,
05:37he readily he was very invested
05:39in Yale and Yale Cancer Center,
05:41and he and he agreed to become
05:43the chair of our scientific.
05:44Advisory Board and then he was
05:47chair of the overall Advisory Board
05:49and then because he suggested it,
05:51he decided it would be good if he
05:53was chair of both at the same time
05:55because he could have an annual
05:57dinner with both boards and and
05:58show each other what we were doing.
06:00It was typical of Paul to do that.
06:02He said he was a good garius and it was
06:04just a wonderful thing to work for him.
06:07I first met him in 1965 when I
06:10was actually working with his
06:13father Massimo over at the VA.
06:15Last night was the head of Cardiology,
06:17so I I go back a long way
06:19with the Calabrisi family.
06:21Paul was a Renaissance man and
06:22the real pleasure to know him.
06:23I miss him often and so I'm happy
06:29to do this and I'm happy to welcome
06:31you Ned to give the Calabrese
06:33lecture I must just say one thing
06:35about your title of your talk.
06:37It's an intriguing title modifying cancer
06:40as we know it suggests that you have
06:43another dimension in bind for evaluating.
06:45Outcomes and cancer.
06:46I look forward to seeing you
06:48unfold this in your lecture.
06:50Thank you.
06:52Thanks Vincent,
06:52and for our fellows from 1:00 to 1:30.
06:55Vince and Ned and the fellows and
06:57the fellowship leaders were gonna
06:58have a little just informal lunch.
07:00You know, virtually just to sort
07:02of have the fellows have a chance
07:03to get some mentorship from the
07:05leaders in the field from the NCI.
07:07OK, let's let's get on to the talk.
07:10I'm sure net is ready to go.
07:13So welcome as I said, you know,
07:15I'm really so happy to invite
07:17the family online today.
07:18The Calabrese family and
07:20I'm especially honored that.
07:22You are here with us today.
07:23Net a year this year is Calabrese lecturer
07:26Paul Calabrese is often referred to
07:27and if we could go to the first slide,
07:29Renee as the father,
07:31please as the father of oncology.
07:33And as influence here at
07:35Yale Cancer Center remains.
07:37A former faculty member at Yusko of Medicine,
07:40he was an internationally recognized
07:42authority on the pharmacology
07:43of anti cancer agents.
07:45Doctor Calabrese serves as director
07:46of yet Cancer Centers Advisory Board.
07:48Is he just heard?
07:50Until 2003 and a personal note,
07:52I had the good fortune to meet Paul.
07:55It says 30,
07:56but it's actually almost 40
07:58years ago as a son.
07:59Peter wasn't.
07:59I guess these are the same
08:01notes we used ten years ago
08:02when I started doing this was my
08:04freshman roommate here at Yale.
08:05Over the years.
08:06Paul was an advisor,
08:07mentor and friend to me,
08:09and it's very meaningful to me
08:10that I now hold the job that he
08:12once held and it's not doesn't go
08:13unnoticed to me that in Room 2 away
08:15I kind of silly during a difficult
08:17meeting or a challenging question.
08:19His face right in front of me
08:21joining us today are the honorable
08:23Guido Calabresi Guido's in Italy.
08:25We don't ask the first question,
08:27as has been our tradition,
08:29so get ready,
08:30Guido and of course calls
08:32Brother and Judge Janice Max,
08:34his daughter and Peter Calabrese
08:36and Steven Calabresi,
08:38his sons.
08:38Thank you all for joining us and for
08:40helping to continue your brother and
08:42father's legacy here at Yale and Peter.
08:45I don't take too much time,
08:46but I know we sent a globe to every member
08:48of the family and some of the speakers.
08:50You should have it,
08:51you just want to say one
08:52quick word before we move on.
08:54Sure, and again,
08:54I don't want to delay the lecture,
08:56but on behalf of our whole family.
08:57Thank you so much Roy.
08:59And everyone at Yale and and thank you
09:00Doctor Sharpless for giving this lecture.
09:02We're very much looking forward to it.
09:04OK,
09:04and now to introduce net and
09:06if we can go to the next slide,
09:07we're honored to have Doctor Sharpless here.
09:09Today,
09:10the director of the National Cancer
09:12Institute to honor 50 years of
09:14the National Cancer Act for him to
09:16share his insights from the NCI
09:18prior to his appointment at the NCI.
09:20Doctor Sharpless served as a
09:22director of the Lineberger Cancer
09:24Center at the University of North Carolina.
09:26Doctor Sharma is Sharp was a Morehead
09:28scholar at UNC Chapel Hill and received
09:30his undergraduate degree in mathematics
09:32who went on to pursue his medical degree
09:34from UNC School of Medicine and completed
09:37his Internal medicine residency at MGH,
09:39Massachusetts General and Hematology
09:41Oncology fellowship at the Dana
09:43Farber Partners Cancer Care.
09:45Back of Sharpness is a member of the
09:47Association of American Physicians
09:48and the American Society for Clinical
09:51Investigation and as a Fellow of the
09:53Academy of the American Association of
09:54Cancer Research, he has authored more
09:57than 160 original scientific papers,
09:59reviews and book chapters,
10:00and as an inventor on 10 patents,
10:02he has co-founded two clinical
10:05stage biotechnology companies,
10:06G1 Therapeutics and Sapphire Bio net.
10:09It's really an honor and
10:10haven't sent this yet,
10:11but I haven't read the next slide.
10:13Please Renee,
10:13I have this lovely plaque that can.
10:15Go right next to Vince's
10:17picture there at the NCI.
10:18Beautiful plaque and for your
10:20office commemorating that you
10:22are our pal breezy lecture.
10:24We're so honored to have you
10:25and now the floor is yours.
10:27We look forward to hearing your remarks.
10:30Thank you, that kind introduction.
10:31It's good to see old friends.
10:32At least virtually.
10:33I wish I could be there in person.
10:35I I love New Haven and and we will
10:37have to take a rain check on this.
10:39I'm I'm really excited today to
10:41do this because for two reasons.
10:42One is, it's an opportunity to talk about
10:44the National Cancer Act and how important
10:46that's been on its 50th anniversary.
10:48But also I I think you know it's
10:49an opportunity to recognize a real
10:51giant among cancer researchers
10:52in cancer caregivers and such.
10:53An important leader in our
10:55field and next slide.
10:57As has been said,
10:58the Calabrese family.
11:00Has a deep connection to Yale,
11:01including a pulse father who was
11:04a cardiologist untold and his mom
11:06had a degree from Yale and we've
11:08heard about Judge Calabrese in his
11:11imminent work and work with Yale.
11:13And we hear about the next generation of
11:15calories having these DPL connections.
11:17Paul Calabrese also had a deep
11:18connection in National Cancer Institute.
11:19He was, I think,
11:21his career actually began doing
11:23field work for the NCI and then
11:25serve the NCI in several capacities
11:27including as chairman of some of
11:29our most important advisory boards.
11:31National Cancer Advisory Board and
11:32the President's Cancer Panel has been
11:34saluted and if the honorable Guido
11:38Calabrese I'm told us here today,
11:39let me offer a heartfelt recognition
11:41to all the Calabrese family for
11:43what they've contributed to Yale
11:44and and improving what I I believe
11:46is the human condition.
11:47Through their work.
11:48I'm early also pleased that
11:50Doctor Devita is here.
11:51Vince is a giant in our field and
11:53has a direct connection to the
11:55what we're talking about today.
11:56The National Cancer Act.
11:58Vince joined the NCI in 1963
12:00and was in CIA director.
12:01From 80 to 88 and a doctor,
12:03Vida has been a a wealth
12:04of good advice to me.
12:05In this role,
12:06I found his book titled the Death of
12:07Cancer Really Interesting Thing to Read.
12:09Before I started inside Erector,
12:10I recall having a very interesting
12:12conversation with Vince about the FDA.
12:15Prior to me going to the FDA to
12:16be acting Commissioner for seven
12:18months and it was really informative
12:19to have that perspective in
12:21the back of my head as I worked
12:23regulating food and drugs.
12:27So I think it's a fitting memory
12:29that we're going to talk about the
12:31National Cancer Act today in given Dr.
12:34Calabrese his connections to it,
12:35his contributions to Cancer Research,
12:37cancer care and the infrastructure,
12:38so to speak, of our research capabilities
12:40made him a real giant or field.
12:42And I'm really talking about
12:43his work and you know,
12:44understanding the pharmacology of cancer,
12:46chemotherapy,
12:46his work in a combining chemotherapy,
12:48other other modalities, his leading
12:50edge research in geriatric medicine.
12:52I think it's very prescient
12:54for a cancer researcher.
12:55His devotion to patient care.
12:56Which is really empowered
12:58his research activities,
12:59his leadership on countless boards,
13:00committees, institutes, academies,
13:01societies and various other governing bodies.
13:04But I think perhaps most importantly
13:06is invaluable mentorship to a
13:07real generation of leaders in
13:09Cancer Research in cancer care,
13:10including among them.
13:11One of my old bosses,
13:12Doctor Bruce Chabner at the MGH at the NCI.
13:16We honor Dr Calabrese contributions
13:17with a specific grant in his honor.
13:20It's the Paul Calabrese Career
13:21Development Award for clinical
13:23oncology and these are K12 grants
13:25that are really designed to prepare.
13:26Oncologists for a second for
13:28effective scientific careers,
13:30and in particular,
13:30by pairing them with basic scientists.
13:32And I was actually the Pi of the university,
13:35North Carolina State Calabrese
13:36award many years ago,
13:38and I know how important an award that is
13:40and it really gets fitting to honor Dr.
13:42Calabrese with the training award for that,
13:44that that that stage of someone's career.
13:46Given his terrific legacy
13:47of mentorship and training.
13:50So today I would like to talk
13:52about the National Cancer Act,
13:54and you know how that changed
13:56from the period of.
13:57Doc Calabrese career to modern
13:59day and I I think the efforts of
14:01Paul along with other luminaries
14:03of the past five decades,
14:04really drove and made possible the
14:06tremendous progress we're seeing today
14:08in cancer care and cancer outcomes.
14:10Their work really provided.
14:14This progress in the past,
14:15but also may possibly these opportunities
14:16that I believe lie before us,
14:18and that really will shape the future
14:20of Cancer Research in cancer care.
14:22Next slide,
14:22I think it's hard to overstate
14:24the importance of the National
14:26Cancer Act in 1971.
14:27For those of you who are younger
14:28who don't know a lot about the NCA,
14:29it did not create the NCI,
14:31so the National Cancer suit
14:32dates back to 1930s,
14:34but I would argue in many ways the National
14:36Cancer Act created kind of the modern NCI.
14:37The thing that we recognize today
14:39as a National Cancer student,
14:40it really united patients, doctors,
14:42scientists, industry and government.
14:43In a common vision and from my perspective.
14:47I think the NCA really did
14:48three important kinds of things.
14:50So First off.
14:50We heard from Vince about how it
14:52provided additional funding for Cancer
14:54Research, and I'm sure that that.
14:56Uh,
14:57extra funding was very important
14:59to doctor Carl Baker,
15:00who is director of the NCI at
15:02the time and
15:02I I think you know a more support
15:04for casters are important,
15:06but I would actually argue that
15:07the funding was probably the least
15:09important of the many important things.
15:10The NCI NCA did it also.
15:13The second type of activity,
15:15the National Cancer Act did was
15:16it gave the NCI a bunch of new new
15:19authorities and created new critical
15:20infrastructure that really led to sort
15:22of some of the modern capabilities
15:23in National Cancer Institute,
15:25so it it encouraged the NCI.
15:27I created a national database of cancer
15:28statistics which led to the SEER program,
15:30which is arguably the most important
15:32set of cancer statistics in the world.
15:34It really created Frederick National Lab,
15:36which is a way of doing research.
15:37The NCI uses it.
15:38You know it really invigorated and
15:40provided the framework for the modern
15:42Cancer Center program that we've heard about.
15:44It made the NCI director presidential
15:46appointee did a bunch of other
15:47things like the President's Cancer
15:48Panel and dash Cancer Riser Board.
15:50Things that were really important,
15:51and I think those authorities and new
15:53infrastructure were really important.
15:54Part of the NCA, but maybe the second most.
15:57Important thing it did and the third thing
15:59that I believe in National Cancer Act did,
16:01and arguably the most important
16:02thing the National Cancer Act did.
16:04Was it made cancer something that
16:06we could talk about this society?
16:08It was it it turned cancer from a
16:10disease that had stigma associated
16:12with it and and and and and a diagnosis
16:15that was sort of HID in the shadows.
16:17And it brought it out into the
16:18light and really spurred the modern
16:21interest we have in Kansas.
16:23Ability to talk about cancers,
16:24ability to work on cancer,
16:25and the modern cancer advocacy meeting.
16:28Movement,
16:28which has been so important so it
16:31was really important to act and it
16:33did things of terrific significance.
16:36But as visionary as the National
16:37Cancer Act was, it was also naive.
16:39Many of the individuals involved
16:41at that time thought we'd have
16:43a cure for cancer very quickly.
16:45You know, 5 to 10 years.
16:46I think this was motivated
16:47by the experience of,
16:48you know,
16:49antibiotics and sepsis in the early
16:5120th century.
16:51And obviously you know that things
16:53didn't workout that way.
16:54Cancer turned out to be a much more
16:56difficult problem than we understood in 1971,
16:58but we now have worked for five
17:01decades to better develop that basic
17:04science understanding of cancer.
17:07And and today we are really having
17:09much better understanding the
17:10molecular underpinnings of cancer,
17:11and that better understanding is paying
17:14huge dividends for patients now next slide.
17:18So there are lots of ways to look
17:20at the remarkable progress in
17:21cancer over the last few decades,
17:24and some of the various takes
17:25on that are shown here.
17:26But I believe that we will look back.
17:29On this period right now,
17:30today as a golden age of Cancer Research,
17:34we really began to take the
17:35basic science understanding of
17:36cancer and apply it to human benefit
17:38and very direct way. And as I said,
17:40we will think about this error today.
17:41The way we think about you know
17:43antibiotics in the early 20th
17:44century for infectious disease and
17:46and it doesn't always feel that way.
17:48I know, I realize that their burden of cancer
17:50American Society is still very significant,
17:52but from my perspective where I sit,
17:54the progress in cancer is really remarkable.
17:57Here are a few lines of evidence so.
17:59On the far left here we see this
18:02decline in cancer mortality.
18:03This started in the early
18:051990s where cancer mortality,
18:06United States and has declined
18:08from men and women since then.
18:10For lots of reasons,
18:11better cancer screening,
18:12tobacco control,
18:12lots of things have conspired together
18:15to lower cancer mortality rates,
18:17United States,
18:17but in recent years this has
18:20really picked up markedly,
18:22and I think in in recent years some
18:23of those massive declines in cancer
18:25mortality are related to better therapy.
18:27So, and, for example,
18:28I've shown statistics here for lung cancer.
18:30Where a bunch of new therapies
18:32kinase inhibitors and you
18:33check one inhibitors radiation,
18:34federation,
18:35surgery,
18:35etc have all led to a remarkable
18:38decline in cancer mortality on the
18:40order of 6% from 2013 to 2016 per year.
18:44So fairly sharp.
18:44Decline in the most lethal cancer in humans.
18:47This has been matched by a
18:49remarkable increase in FDA approvals
18:50of drugs and devices and other
18:52medicines for cancer patients who
18:55markable period of productivity.
18:56I can remember when I started
18:58as a fellow in this business,
19:00you could go a whole decade.
19:01Not really have amazing new drugs
19:03approved in cancer care and
19:05now it's it's a monthly event.
19:06At the FDA there was a period
19:08in 2020 and one month where I
19:09think we had seven lung cancer
19:10drugs approved in the same month.
19:12So really and and not be too not
19:14useful drugs, but really a paradigm,
19:16changing new therapies and and
19:18I think there's real scientific
19:19excitement in in Cancer Research.
19:21And that's shown down at the
19:22bottom right here.
19:23And that's the graph of applications
19:25to the National Cancer super funding.
19:27We can see this massive increase
19:29since 2013 a on nearly 50%.
19:32Increase over about a seven year
19:34period and applications for funding the
19:36NCI and this is a mark that you know.
19:38People have great new ideas for
19:40cancer therapy and are coming to our
19:42field with new proposals and new ways
19:45of treating cancer that include.
19:46You know physicists and mathematicians
19:48and other kinds of biologists and
19:51working with a new clinical approaches
19:53and all seeking support from National
19:56Cancer suit for their research.
19:58This also creates a problem.
19:59I'll be.
20:00I would argue a good problem which
20:01is tremendous.
20:02Competition for funding at the NCI.
20:03So Vince mentioned the 50% success
20:06rates for grant funding back in his era.
20:08It was as low as 8% earlier in my
20:11career at NCI.
20:12We have now through a fairly
20:14Herculean measures.
20:15Gotten it up to 11%, but you can see
20:17that is still a very low success rate
20:19for grants at the NCI and something
20:21we're deeply concerned about because
20:22that is the pool of grants where the
20:24really paradigm changing ideas come from.
20:27The things that really move the
20:28field for patients so you know,
20:29in in improving support for,
20:31investigated, initiated science.
20:33Remains a top priority for the NCI.
20:37I think many Americans have heard of these.
20:39You know, advances and it really
20:41take them for granted.
20:42It's like computing power,
20:44automobile mileage.
20:44We just sort of expect these things to
20:46get better indefinitely and not realize
20:48all the work that went into that.
20:49But that was not the case.
20:51As I said in 1971,
20:52that wasn't even the case in the early 1990s.
20:54It's really become a feature, uh,
20:57more recently, and that as I said,
20:59is really built on the molecular
21:01understanding of cancer biology that
21:03we've developed in the past 50 years.
21:05And now I think we should talk
21:07about where we go from here.
21:08How we use this progress at the last five
21:11decades as a bridge to the to the future.
21:13And this next period of bridge building
21:15will build on that momentum that we've
21:17established over the last 50 years.
21:18But it will not just but but.
21:21And it's not just this momentum of
21:23the fundamental understanding of
21:24cancer and this knowledge base that
21:26with the keen scientific insights of
21:28those on whose shoulders we stand now,
21:30people like dark dark Calabrese and
21:32Doctor Devita and so for that 3
21:33minutes I'd like to talk about how
21:35we're going to build that bridge
21:36to the future.
21:37Building on this progress next slide.
21:40So what motivated my talk is titled
21:42today is a quote that's been made
21:45frequently by the President,
21:47Doctor President Biden has said
21:49many Times Now that he'd like to
21:51end cancer as we know it,
21:52and I think Paul Calabrese would
21:54be gratified to know that we have
21:56this President in the White House
21:57with his with an intimate connection
21:59of Cancer Research.
22:00Who knows what our work means for
22:02the American Public,
22:03President Biden and the First lady have
22:05a very strong personal connection to cancer.
22:07We are the story of their sons.
22:10Definitely Blastoma is
22:11well known to all of us,
22:12and they're also firm believers
22:14in the power of Cancer Research.
22:16The tragedy that befell the Biden
22:17family led to then Vice President
22:19Biden's leadership of the Cancer
22:21Moon shot six years ago,
22:23and the current administration,
22:24as I said,
22:25is calling for all of us collectively as
22:27a community to end cancer as we know it.
22:29We think that this problem is
22:30much bigger than just the NCI.
22:31The NCI is obviously part of this,
22:33but this would require all the powers
22:34of both the federal government,
22:36but also advocacy and caregivers outside
22:38of the federal government in considering.
22:40The achievements of the past
22:4250 years and
22:43how to steer the future of Cancer Research.
22:45We've been thinking this through at the NCI.
22:46What does it really mean to
22:48end cancer as we know it?
22:49So you have to think about
22:50how do we know cancer today?
22:52What would it mean to change
22:54that experience of cancer?
22:55And what would that take?
22:57First, let me let me be clear.
22:59There is no mention of eradicating
23:00all cancer I think based on what
23:02we know about human biology today,
23:04we don't believe that's possible.
23:05The NCI, at least anytime soon.
23:08But we do think we could dramatically
23:09change the experience of cancer.
23:11That is the tragedy of cancer.
23:12The way the American public
23:14knows cancer today and to get it.
23:17This we we we have to be upfront
23:19about the uncomfortable realities
23:20about cancer as we know it today.
23:22So I mentioned a lot of the
23:24progress and that progress is very
23:26exciting and it's been very good.
23:27But we still have a long way
23:29to go in the United States,
23:30600,000 Americans still die
23:31from cancer each year.
23:33Cancer is still the leading
23:34cause of death from children in
23:36children from death and disease.
23:37Cancer costs the nation hundreds
23:39of billions of dollars every
23:40year in terms of treatment.
23:42And lost productivity.
23:42And even when we're able to cure
23:44patients with cancer too often
23:46this comes at the cost of severe
23:48treatments with significant long
23:49term toxicities and cancer for many
23:51patients is still a very devastating
23:53and life changing diagnosis and for
23:55people with a new diagnosis of cancer,
23:57you know telling them about all
23:58this great progress last 50 years.
23:59That's really small comfort.
24:01They don't really want to hear from
24:03the NCI director about the record
24:04number of grant applications or FDA
24:06approvals or new infrastructure.
24:08They really like to see a cures,
24:10or at least better treatments for their
24:11cancer that for their for their disease,
24:13which provides them more time.
24:15I once treated a woman in her in her
24:17early 40s for metastatic triple negative
24:19breast cancer and we tried sort of the
24:22usual therapies and it wasn't working.
24:24It wasn't going well and we were
24:26discussing what therapy to try
24:27next for her and I did what we
24:29train our junior oncologist to do.
24:30I asked her what?
24:32Her goals were for more therapy.
24:34You know, I said,
24:34what do you want to get out of
24:36this next round of treatment?
24:37And as I said,
24:38we this is something we inculcate
24:39in our medical students and we
24:40sort of beat this habit into the
24:41residents and fellows to ask the
24:43patient what they want from therapy.
24:44It's an important thing to do,
24:46but in some ways it's also kind
24:47of A dumb question, right?
24:49It's no mystery what our patients want.
24:51They generally want better
24:52treatments for cancer.
24:53They want to cure for their cancer.
24:54They want their cancer to go
24:55away and never come back.
24:56So the goals for therapy
24:58are usually pretty obvious.
24:59What we're really doing in this
25:01period is is trying to get.
25:02To understand what's possible about
25:04sort of managing expectations based
25:06on what we believe we can deliver.
25:08So this patient told me.
25:10That she knew she would die of games
25:12where she knew she had untreatable
25:14or refractory metastatic disease and
25:16she had no illusions to being cured,
25:18but she wanted more time.
25:20She had three children who were sort
25:21of middle school age at the time,
25:23and her goal of hers was to see
25:25them graduate from high school.
25:26And that's sort of all she wants.
25:27A few more years.
25:28It didn't seem at the time
25:30like an unreasonable request.
25:31Given all this progress and
25:32work we've had in cancer,
25:33but we couldn't even do that for her.
25:35She died really about a year later.
25:38I've argued many times many times
25:40before that many of us in the
25:43cancer community have become afraid
25:44about talking about curing cancer.
25:46I believe I made this exact
25:48point at Yale in 2017.
25:49Soon after I became inside erector.
25:51I know why using the word cure
25:53around patients causes so
25:54many problems for caregivers.
25:55I understand the the worry about
25:57providing false hope and empty promises,
25:59and I know that we have gotten
26:01into the habit of qualifying our
26:02language all day long of caveats
26:04and disclaimers and talking about
26:05things like disease free survival
26:07and and remission and and whatever.
26:08Metrics, sort of in vogue that day,
26:11but, uh, but patients.
26:12I think we should be clear still
26:14want to be cured of their disease.
26:15And if that's not possible,
26:16they want their cancer be turned
26:18into a manageable chronic disease,
26:20so they'll have more quality
26:21time with their loved ones.
26:22And so that's really what we're
26:24talking about when we say
26:25ending cancer as we know it,
26:26or knowing cancer today.
26:27And that's what the president wants us to do.
26:30Next slide.
26:32So National Cancer St.
26:33We've been thinking a lot about
26:34what this means to like no
26:36cancer in some way and and here,
26:37and one way to think about this as
26:39things that are true about cancer today.
26:40These are true statements that we
26:42would like to make untrue in some way.
26:45If we could make these things untrue,
26:47then in doing so we would change cancers.
26:49We know it.
26:50So I've spoken at length already
26:51about cancer mortality that in
26:52this box here in the lower left
26:54I gave a lecture last April.
26:56ACR,
26:56when I described how I believe a
26:58strong reduction in cancer mortality
26:59is possible building on momentum
27:01we've seen in the last 30 years.
27:03I talked about the things that we
27:05could do to try and cut cancer,
27:08age adjusted mortality in half
27:10from its peak in 1992.
27:12You know half of that in the next few years,
27:16and some approaches that one could take
27:17to try and get there quickly as possible.
27:19And so you if you think about that,
27:20those are things that would really
27:23drive down aygestin mortality
27:24quickly, and you can say this is really the
27:26ultimate measure of our progress of cancer,
27:28is how many people are dying in cancer.
27:30But yeah, there is a lot more to the
27:32experience of cancer than just mortality.
27:34And today I wanted to focus on some of those
27:36other topics that we talked less about,
27:37and so a few of those statements
27:39are shown here. So, for example,
27:41we have two few ways to prevent cancer.
27:44Many treatments are so toxic that they're
27:47intolerable and cause lifelong morbidity.
27:50Too many patients are stymied,
27:51stymied by the complicated
27:53logistics of cancer care and and,
27:55and and and, and create these
27:57disparities because of access to care.
27:59And I know we can all think of other
28:00statements that are true about cancer.
28:02Things that we'd like to
28:03make untrue about cancer.
28:05I believe it's with our power deliver on
28:07the president's call to action to confront
28:09the current reality of cancer and raveling.
28:11To take today's in many ways,
28:12sad reality and realize a better future.
28:15In the months ahead,
28:16I want all of us to catch you to consider the
28:18steps we can take to solve these problems,
28:20as we've solved many other related
28:22problems over the past five decades.
28:23I don't really have time to
28:25develop delve into all of these,
28:26so I thought I'd pick a few to talk about,
28:27and the ones that I boxed here are the areas
28:30where I'd like to focus some examples today.
28:33As mentioned,
28:33we've already talked about mortality a bit,
28:35so I thought I'd take on.
28:38Early detection and screening,
28:40health inequities and
28:42refractory and rare cancers.
28:45Next slide.
28:47So in 1971, cancer screening and
28:49detection was really in its infancy,
28:51but we know now know that screening
28:53and early detection are really
28:55powerful tools for improving cancer
28:56outcomes in both individuals,
28:58but also at the population level.
29:01It's clear that development of effective
29:03screening approaches has been transformative,
29:05but we think things are really
29:06early in this field still,
29:07and believe screening and detection could
29:09be even more impactful than they are today.
29:12So now we have effective screening
29:14tools for for cervical cancer,
29:16breast cancer, colorectal cancer,
29:17and lung cancer.
29:19And even though they're uptake is
29:20not as good as we would like it,
29:22specially by the way for lung
29:23cancer screening modalities for
29:24these diseases have had a dramatic
29:26impact on US cancer mortality.
29:28Already I spoke with someone recently
29:30who had been described had been
29:32diagnosed recently with early stage
29:34breast cancer with screen detected
29:36breast cancer found in mammography,
29:38and she described to me what
29:40an inconvenience this was,
29:41how it had been a little frightening
29:43at first,
29:43but then it just had become more of
29:45a hassle she'd had sort of a minimal
29:47surgery at a brief course of radiotherapy.
29:49And was told that she would
29:51enjoy an excellent prognosis.
29:52And that's really the kind of experience
29:54we want to see for more types of cancer.
29:56I mean,
29:57Can you imagine anyone in
29:581971 talking about you know,
29:59a diagnosis like that being an inconvenience?
30:01You know now that's a problem that is,
30:04in some ways a good problem,
30:06but even after many advances in
30:07detecting and treating cancer,
30:09being couple reality is that we still
30:11lack effective ways to detect many
30:13types of cancer before they spread
30:14and become more difficult to treat.
30:16And the cancer types,
30:17with some of the worst outcomes,
30:18frankly, are those where the
30:20disease can only be detected,
30:22typically when it's too
30:23late to treat effectively.
30:24Think you know pancreatic
30:25cancer in glass Dome,
30:26etc.
30:27Next slide.
30:29One cancer is an area where the National
30:31Cancer suit works should be highlighted.
30:33It's had an important impact on early
30:35cancer screening and early detection.
30:36I think this group will be aware of the
30:38national lung cancer screening trial,
30:39which was a landmark study led by
30:41the NCI that show that CT scanning
30:43could reduce mortality from lung
30:45cancer in specific populations
30:46related to age and history of smoking.
30:48This result was confirmed by a
30:50similar European trial and asked
30:52low dose CT screening is really
30:54considered the standard of care
30:55for patients of certain age with
30:57certain history tobacco use.
30:58As an effective means of reducing
31:01lung cancer mortality,
31:02and this is an example of how we can
31:05rigorously test an approach and move
31:06it into broad community practice and
31:08then refine it further through their study.
31:10This is really also an important
31:12illustration of some very critical
31:14nuances related to cancer screening.
31:16So,
31:16for example,
31:17the screening guidelines that
31:19were finally established in 2013
31:21by the United States Preventive
31:22Services Task Force
31:23USPSTF excluded large numbers of
31:25patients from screening because
31:27of the cut offs that were chosen
31:29in this particularly applied.
31:30To women and African American individuals
31:32who had lower smoking histories,
31:34not not as many Packers.
31:36And these individuals hadn't hadn't
31:37smoked enough to make the cut offs,
31:39but they nonetheless faced a higher
31:41risk of dying from lung cancer.
31:42So the NCI sought to address this issue
31:44by performing a modeling in arsis.
31:46Net network,
31:46and we concluded that screening
31:48guidelines should be amended to
31:50protect patients with even a more
31:52modest history of tobacco use,
31:53and based on that work,
31:54the latest revision of the USPSTF guidelines
31:57for lung cancer lowered those thresholds.
31:59A change that is a particular benefit that.
32:01Female African American smokers that are
32:03now eligible for screening a side note,
32:05by the way, similar recent USPSTF change
32:08was made to colorectal screening,
32:10colonoscopy and colorectal
32:12screening guidelines.
32:13Also based on NCI sponsored cisnet modeling.
32:16So the main problem right now with lung
32:18cancer today is vastly underutilized.
32:20For reasons that I do not
32:22completely understand,
32:23we've modeled what a more robust
32:25uptake of lung cancer screening could.
32:27It could mean in terms of overall
32:28cancer salary, United States,
32:29and it's a real opportunity.
32:31And the NCI funding mini opera mini
32:33studies in this sort of this field of
32:35dissemination and implementation science
32:37to understand why an effective screen
32:39modality is so vastly underutilized.
32:41But I think the story of lung cancer
32:43screening shows how the NCI can
32:44play a really important role in
32:46developing the preliminary science,
32:47disseminating that greater and then
32:49refining these recommendations.
32:50All for public health benefit.
32:52A next slide.
32:54So broader adoption of proven methodologies
32:55like history will be important,
32:57but they're also exciting.
32:59New technologies for early cancer detection.
33:01One particular approach are these so called
33:04multi cancer early detection tests or embeds.
33:07The idea here is a single test,
33:09usually a blood test done on otherwise
33:11healthy individuals at some regular interval.
33:14Think yearly to diagnose several
33:16cancers at once by detecting features
33:18of the cancer in a single analyte.
33:20They two of blood,
33:21and there are really many many
33:22approaches to this.
33:23There's DNA methylation.
33:24Their cell free DNA,
33:25there's exosomes etc etc.
33:26I I believe this concept holds great
33:29promise and these technologies
33:30are evolving rapidly and entering
33:32large scale clinical testing as we
33:34speak and I think these approaches
33:36could potentially reduce cancer
33:37mortality at the population level,
33:39but they have to be rigorously evaluated
33:41in a timely manner as I think this
33:43group is where cancer screenings
33:45are treated business because there's
33:46always this worry about overdiagnosis
33:48and overtreatment and the ability to
33:49harm patients through cancer screening
33:51and so evaluating these technologies
33:53will be challenging parenthetically.
33:55For those of you been following around.
33:56Following news in the in in in in DC we
33:59have heard about this new entity called RBH,
34:02which at this point is still a
34:03proposal of being taken up by
34:05Congress to create a new agency akin
34:06to DARPA and DARPA. The Defense
34:08Advanced Research Projects Agency.
34:10So our pH would be the Advanced Research
34:12Projects Agency for health and this
34:13would be within the NCI but with
34:15different structures and authorities
34:16to enable the rapid development
34:17of high risk high reward projects.
34:19And I, I believe in others have
34:21also stated that our page might be
34:23a good instrument for evaluating
34:25a new technology like this.
34:27As there is this very pressing need
34:28to evaluate these technologies
34:30as soon as possible, next slide.
34:33Let me turn to another major problem
34:35that we have failed to adequately
34:37address and that that is cancer.
34:39Health disparities and inequity
34:40in health and cancer care,
34:42and this is a whole constellation
34:43of issues that Dr.
34:44Disparities in outcome for
34:46outcomes for our patients.
34:48We face important disparities in
34:50cancer diagnosis and treatment,
34:51trial access,
34:52and any outcome based on race region.
34:55Access to care associated
34:57with status and other things.
34:58In other words,
34:59different demographic groups are
35:01affected differently by the health
35:02challenges they face and the
35:03circumstances in which they face.
35:05They think about the challenges that
35:06many people with cancer face and how
35:09their specific circumstances impact
35:10their care and their experience.
35:12So Sherry Davis is a patient.
35:14The NCI knows you need cancer
35:15treatment in Florida,
35:16but couldn't find a Doctor Who take Medicaid.
35:18That was closer than three counties away.
35:21And another patient,
35:21Barbara Ingalsbe,
35:22drove 100 miles every weekday
35:25for radiation treatment.
35:26And several states away we had
35:28Albert Callaway who had a neck
35:30tumor that grew and grew because
35:32this individual was uninsured and
35:34was overwhelmed by the process of
35:36trying to figure out how he fit
35:38within the health care system.
35:40These are three real patients,
35:42and it's clear that experiences like this.
35:43United States are entirely too common.
35:45While we've made great progress for
35:47overall in Cancer Research care,
35:49these benefits have not reached
35:51all people equally.
35:52So the NCIS long sought to address
35:54cancer authorities and we were working
35:55in this area even before that term.
35:57Health care disparities really
35:58was available in research,
36:00but of course recent events and I'm
36:01talking about the death of George
36:03Floyd and the disproportionate
36:04impact of the pandemic on the
36:05poor and disenfranchised.
36:06These recent events have
36:07injected and rightfully so.
36:08I believe a new focus.
36:10Passion and commitment to addressing
36:11disparities in the entire NIH,
36:13including the NCI.
36:14That said, these problems are very
36:16hard if their answers were easy.
36:18We have solved by now.
36:19Next slide.
36:21Cervical cancer is an interesting
36:23example of the complexity of
36:24cancer health disparities.
36:26So here is a graph showing the
36:27incidence of this disease overtime,
36:29and it shows a very positive trend.
36:31There's been this remarkable decline
36:33in cervical cancer incidence in the
36:35United States over the last few decades,
36:37and we have completely eliminated
36:39the difference in incidents.
36:40Between African American and white women,
36:42and this is good news and it
36:44reflects increased screening for
36:46cervical cancer as well as an
36:48effective HPV vaccination.
36:49And while we should celebrate
36:50this progress with regard to this
36:52important health care disparity,
36:53we should also note that at
36:54the same time that a very large
36:57difference in mortality from
36:58cervical cancer still exists today.
37:00So even today, black women in EU
37:01S or more than 50% likely to die
37:03of this disease than white women.
37:05So first I think is a scientist.
37:06You have to admit this is interesting.
37:08How can we have so much progress
37:10against incidents and mortality?
37:12And why is this cancer so much more
37:13lethal in black women and white
37:14women and white can invoke a lot
37:16of explanations for this could be
37:17differences in biology or differences in
37:19risk factors or differences access to care.
37:21Structural racism in the healthcare system.
37:23All of these explanations have
37:25plausibility and in cancer helps parities.
37:27Let me tell you,
37:27it's generally not one of these.
37:28It's going to be a combination of.
37:30Multiple things creating these disparities,
37:32but it's really the business of the National
37:34Cancer Institute to figure this out.
37:35We should support the research
37:37that would indentify the causes
37:39of these disparities and,
37:40and that's really the key to address to
37:42fixing these problems and next slide.
37:45Race and ethnicity are two features
37:47of society that drive healthcare,
37:48cancel disparities.
37:49But there are many other
37:51important contributors.
37:52Increasingly,
37:52we're appreciating that cancer
37:54outcomes are driven by geography,
37:56which we think is related to access.
37:58For example,
37:58we know that people live in rural
38:00communities have worse cancer outcomes
38:01regardless of race, ethnicity,
38:02cancer incidence and mortality overall or
38:05higher in rural areas than urban ones.
38:08This is not always been true
38:08in the United States.
38:09In the early 1990s,
38:10rural patients did better
38:12than urban patients,
38:13but that that trend is reversed
38:15and the disparity between.
38:16Her in urban and rural patients
38:17gets worse every year.
38:19This observation holds true
38:20for cancer overall,
38:21but particularly for cervical cancer,
38:22colorectal cancer, kidney cancer,
38:24lung cancer,
38:24Melanoma and oropharyngeal cancers.
38:26Along these lines,
38:28a recent study from NCI grantees
38:30published this month revealed that
38:31women residing in urban areas were
38:33significantly more likely to get
38:34the recommended colorectal cancer
38:36screening compared with women in
38:37rural states. Areas of 11 states.
38:40However,
38:40both groups had similar rates of
38:42adherence to breast cancer screenings
38:43for showing how complex this is.
38:45So you sort of get a different effect
38:47of reality on colorectal cancer
38:49screening versus breast cancer screening.
38:51That is,
38:52colonoscopy versus mammography,
38:53but perhaps the most important thing
38:55to realize about health spirit research.
38:58Is really the need to stop solely
39:00focusing on a single feature of these
39:03complex heterogeneous populations.
39:04So shown here is is a beginning
39:06to try and get a handle on this.
39:07This is the topic of persistent
39:10poverty which is defined as 20%
39:12of the population living below the
39:14poverty threshold for decades and we
39:16note that the outcomes of patients
39:18living in areas of persistent poverty
39:20are worse than patients who are
39:21living in areas that are
39:23merely currently poor.
39:24That is their socio economically
39:25the same today. But one is that
39:27structural poverty going back.
39:28Decades and that population does worse,
39:31so no social economic status alone.
39:35Can't really capture what's going on here,
39:36and we need more sophisticated
39:38approaches to understand this
39:40interaction between morality and poverty,
39:42particularly through time.
39:43We have other examples, for example,
39:46the example of American Indians were
39:48overall cancer outcomes are not that bad.
39:51But in in certain the interaction with
39:53poverty in that population is particularly
39:55adverse and we see these terrible pockets.
39:58Of very poor outcomes in the
40:00American Indian population,
40:01for example.
40:02So we have lots of data now
40:03showing these sort of non-linear
40:05enter interactions between like
40:06things like race and ethnicity and
40:08genetics and poverty in reality.
40:09And these interactions can produce
40:11some really counter intuitive
40:12effects and so really we think the
40:14NCI a key for cancel disparities
40:15is to stop sort of single variable
40:17analysis and start working on these
40:19populations in their totality with
40:21all their complexity our next slide.
40:24As mentioned a NCIS been interested
40:26in the topic of health disparities
40:28in minority health for some time.
40:30This shows a trend in our funding
40:32in the for these topics.
40:33Dating back to 2010,
40:35the NCI has had a significant spin
40:38in this area for over decades,
40:40but you can see that as sharply
40:42increased in the last few years.
40:44Although this is a large investment
40:46in this area of science,
40:47we believe it is very important to
40:49continuously monitor this portfolio
40:50and we think it's fair to ask
40:51if we're spending on the right.
40:52Topics were asking the right
40:54questions on the field.
40:55For the field and should we be
40:56even spending more in these areas?
40:58We also know that Cancer Research workforce,
41:00the scientists and doctors that do
41:02the cancer science that workforce
41:04does not reflect the population
41:05of the people we serve.
41:07And we've really redoubled our
41:08efforts to make headway against
41:10the problem of under representation
41:12within the Cancer Research workforce.
41:13We all share responsibility to change
41:15this in whatever way we can and bake
41:18HealthEquity into sort of everything
41:19we do and how we that's how we help.
41:21We believe an important
41:22key to ending cancers.
41:23You know it, the president's goal.
41:25Next slide.
41:27Given the lack of diversity in
41:29the Cancer Research workforce,
41:30I am excited about several efforts
41:31from the NCI to address this problem,
41:33so one that is reasonably well
41:35known as the NCI Secure program.
41:37This is the continuing umbrella
41:38of research experiences.
41:39This program is a pipeline
41:40program if you will.
41:41That starts sort of in middle
41:43school or high school,
41:44and it provides support for individuals
41:45all the way to the junior faculty level.
41:48It has thousands of alumni,
41:50some of the most famous researchers
41:52and cancer.
41:53Going today are alumni of the
41:54of the Cure program and really
41:56change trains them for success.
41:57And it is the idea that a pipeline is a
42:00way to address the lack of
42:02representation in science.
42:03Another effort that is different that
42:05is really exciting is shown here.
42:06And this is the first initiative.
42:07So first stands for the faculty
42:10institutional recruitment for
42:11sustainable transformation.
42:12This is a common fund initiative,
42:14meaning it's led the money to support.
42:17This comes from the NIH,
42:18but is led by the NCI working in
42:20collaboration with the National
42:22Institute on Minority Health
42:23and Health Disparities in IHD.
42:25The purpose of the first cohort
42:26is to transform the culture.
42:28At NIH funded external institutions
42:30by building a self reinforcing
42:32community of scientists committed to
42:34diversity and inclusive excellence.
42:36The rationale here is that a
42:38cohort model of faculty hiring,
42:39sponsorship,
42:40and mentoring will lead to really
42:42sustained support professional development
42:44embedded within an institution that's
42:47committed to workforce diversity.
42:49Here is the sort of first set of award E.
42:51There are two more rounds of this coming.
42:53In fact,
42:53the next round of grants is due soon.
42:56You see it as a coordinating center
42:57at Morehouse and then six Ortiz.
42:59And it's an experiment in
43:00this cohort approach,
43:01which will include significant
43:03data collection.
43:04To see if the scientists,
43:06the faculty trained through first,
43:09will benefit from this program,
43:11and so so you see the NCIS invested
43:13in the cohort approach with first and
43:15with the pipeline approach through cure
43:17and we are really trying to consider
43:20whatever approach might work best in
43:22terms of developing faculty diversity.
43:24Next slide.
43:26Let me also talk a little bit about
43:27rare and difficult to treat cancers
43:28just as our advances in Cancer
43:30Research have not benefited all populations.
43:31Our progress has not been even across
43:33all cancers types you see here.
43:34Senator McCain,
43:35who died of Blastoma,
43:37Ruth Bader Ginsburg,
43:37who died of pancreatic cancer.
43:39Chadwick Boseman,
43:40who died of early onset colorectal cancer.
43:44We are seeing an alarming rise
43:46in the rate of colorectal cancer
43:47and lung pain in young patients.
43:49For reasons that are not clear,
43:50the five year survival rate for glioblastoma,
43:53that which affected Senator McCain
43:54is less than 7% pancreatic cancer.
43:56It's less than 11% so.
43:58But among these stories,
44:00you also see in the upper left corner.
44:02Here, a little girl named Brianna,
44:03who had infantile fibrosarcoma,
44:06which was here to forward terrible disease,
44:09but she was treated with Larry
44:10Trek net eight REC inhibitor that
44:13allowed her to avoid amputation.
44:15So hers is a success story in a
44:17rare cancer that speaks to the
44:19long arc of basic science discovery
44:21to successful clinical advance,
44:23the story of Trek inhibitors
44:24for those of you know,
44:25it begins really at the NCI at Frederick
44:27National Lab back in the 1980s,
44:29when Mariano Barba said working as a
44:31contractor was hunting for oncogenes
44:32and he found one called on Cody,
44:34which was later turned out,
44:36shown to be the first fusion known in
44:38cancer and involving the trek gene in 2018.
44:41Layer Trek nib,
44:42which was used in Rihanna's cancer,
44:44was the first drug.
44:45Approved to treat interact few gene
44:47fusions and it is quite a successful
44:49drug for those rare patients that
44:51have those events. Next slide.
44:54Another nice example is the good dark trial.
44:56This is the NCI dual anti CD48PD1 blockade
45:00in rare tumors trial it's the first
45:02immunotherapy trial focused on rare cancers.
45:04Here you know dark trial is been
45:06tried in many different rare cancers.
45:09Here are the results in angiosarcoma
45:10where you can see a patient with a quite
45:12bad tumor involving the face and nose.
45:14With this very nice response to
45:16combine the immuno oncology approaches.
45:18These results are impressive and encouraging.
45:21You can see in about 1/4 of the patients
45:23there are these very impressive responses.
45:25With some patients having their
45:26cancers go away entirely,
45:28this is a remarkable for a number of ways.
45:31For reasons we a subtype of angiosarcoma
45:35been identified earlier through the
45:37count Me in initiative that included a,
45:40you know about 25% of patients that had
45:42high tumor mutational burden and would
45:44therefore be a candidate for immuno oncology.
45:47And then this trial happens almost within a
45:49year to confirm activity in some patients.
45:52A dart is an important platform.
45:54It is not as I said, slowly.
45:55Restricted to angels or comma?
45:57It's looking at other rare
45:58subtypes of cancer.
45:5953 cohorts in all, including
46:01cancers of the ovary and intestines,
46:03and lung and sinus is just rare.
46:04Cancers,
46:05wherever they may be found,
46:07and we think that this is the kind of
46:09approach that really has to be taken
46:11for these kinds of rare cancers on
46:13imitable to traditional clinical trials.
46:15Next slide.
46:16The match trial?
46:18Uh,
46:19employees this basket approach
46:21when match started.
46:22The idea was to sequence patients with
46:24refractory cancer and then allocate them
46:26to therapy in one of the 40 treatment arms.
46:28Based on the molecular genetics of the tumor.
46:31And when we started,
46:32we thought this might appeal to some
46:34patients with rare and uncommon cancers.
46:36But in fact the trial really
46:38exceeded our initial expectations,
46:40with about 60% of those enrolled
46:42on match having cancers other than
46:44colon rectal breast, non small,
46:46cell, lung or prostate.
46:47So it really is preferentially
46:49enrolled patients from this sort
46:51of less common cancer types,
46:53and it turned out to be a great rare cancer.
46:55A framework match,
46:57for example,
46:59is shown promising results in treating
47:01her two amplified salivary gland
47:03tumors are rare cancer subtype and
47:05treating these patients with T DM1
47:07producing significant shrinkage,
47:09significant responses,
47:10every fraction of patients matches.
47:12Also remarkable is one of the
47:13fastest enrolling clinical trials
47:14that were done at the NCI.
47:15Enroll patients 1100 sites in 6000.
47:17Patients in just a few years,
47:19and so I think things like match and
47:21dark really established this basket.
47:23Trial approaches being quite
47:24successful and next slide.
47:27Childhood cancer is is a collectively rare,
47:29comprising approximately 1 three
47:30percent of cancers diagnosed
47:32in the United States.
47:33But this rarity is,
47:34as I said,
47:35no comfort to anyone who's watched
47:37the child suffer from cancer
47:38to treat and it's treatment,
47:40and it makes our quest to end
47:42childhood cancer challenging.
47:43There just isn't enough data in any
47:45sort of 1 tumor type to really do some
47:47of the traditional problem we think of,
47:49and so one effort is trying
47:50to address this problem.
47:51Is the childhood cancer data initiative.
47:53This is a 10 year effort that's
47:55it's really just begun.
47:56Its in its second year.
47:57And the idea here is to trying
47:59to radically aggregate data from
48:01children with cancer to make them
48:03maximally informative for research
48:04and for improved clinical care.
48:06Two important parts of the CCDR shown here,
48:08the childhood molecular
48:10characterization protocol,
48:11which would sort of establish
48:12a floor of molecular analysis
48:14available to every child with cancer,
48:16United States and then a national
48:18childhood cancer registry shown
48:19on the right which would try and
48:21learn from every trial that would
48:22get some data through integration
48:24of registry data and various other
48:25sorts of datasets that we have.
48:27To try and get an idea of what happens,
48:29we experience of cancer is for
48:31alter with cancer, United States,
48:32and we think these are really important
48:35efforts to try and do better in childhood.
48:37Cancer,
48:37a collection of rare diseases.
48:39Next slide.
48:42So having discussed some of the challenges
48:45we face cancer as we know it today,
48:47the reality is that we still need more
48:49progress for the group to early detection,
48:51disparities, and advances in in
48:53rare and difficult to treat cancers.
48:56There are some questions to the
48:57slide that are equally important
48:58that I haven't touched on that,
49:00and I haven't touched on today,
49:01but really I think they they
49:02sort of spur us to think about
49:04what the future will look like.
49:05What are we working toward?
49:06If we're building a bridge
49:07to the future of cancer,
49:08what's on the other side of that bridge?
49:10A world where these statements
49:11are no longer true?
49:12Where we will have changed cancer
49:14as we know it and I I think that
49:17future is within our reach.
49:18Let's focus on a future where all
49:20people with cancer have the support
49:22resources needed to navigate their care.
49:23Let's build a reality in which your
49:25location or your race or your education
49:27doesn't predict the outcome of your disease.
49:29And let's take what we've learned
49:31and and create tests they did.
49:33If I cancer its earliest stages and let's
49:36ensure that once these cancers are detected,
49:38each cancer can be treated,
49:39treated effectively,
49:40and how we're going to do that next slide.
49:43This is what the NCI thinks will take
49:45what it will take over this next period.
49:47You know we've had this 50 years of progress.
49:48Now we need to build on that 50
49:49years of progress to advance health
49:51equity to personalized cancer
49:52care to embrace new technologies,
49:54innovations to inspire the next
49:56generation of cancer researchers,
49:58and to prepare for the challenges
50:00of the future.
50:00This is a set of guideposts
50:02the foundations on which will
50:04build this bridge to the future.
50:06I would argue that we need to look at
50:07all our work through a lens of HealthEquity.
50:09We need to ask to what extent might this
50:11study reinforce existing inequities?
50:13Or might reflect hidden biases and you
50:15can clearly see how these guideposts
50:18are interwoven and overlapping,
50:20and building the next generation
50:21of diverse researchers as part of
50:24embracing innovation and creativity.
50:25Next slide.
50:26Today in our age of rapid progress
50:29and technical and medical advances,
50:31it may be easy to discount the
50:33importance of the National Cancer Act.
50:35But as 1776 was our nation's history
50:38and 1969 was the Apollo program that
50:40put humans on the moon, so 1971,
50:43really I began marks the modern
50:45era of Cancer Research.
50:47Maybe this comparison strikes
50:48you as a little bit over the top,
50:49but I do not believe that is so
50:51ending cancer as we know it will be
50:53a bigger deal for community were as
50:55big a deal for humanity as landing
50:56someone on the moon.
50:58In 1971,
50:58is really what got it started and
51:00that's why that aniverse dissenters
51:01is so important.
51:02It was signed into law at a time
51:04of great need for those people
51:05who feared cancer so much.
51:07Which of the time was basically everyone
51:09the NCA first 50 years was the work of
51:11people like Mary Lasker and optimistic
51:13politicians and pioneering ecologist
51:15researchers were visionary as I said,
51:18but also naive. As I said,
51:19the optimism induced by the legal mandate
51:22and strong infrastructure was soon
51:23tempered by the realization that its
51:26objective was going to be so challenging.
51:28The years ahead will be sharper and focused
51:30different in tone and more practical,
51:32more cognizant of the size and timelines
51:34of these challenges, and more based on
51:36the foundational molecular biology,
51:38biological understanding cancer
51:39over the past five decades.
51:41Many of this is declared.
51:43This time is different,
51:44but they weren't wrong and that's
51:45what's brought us so far to date.
51:47Each time we try this is different.
51:49It was, reportedly Heraclitus,
51:50who observed that no one ever
51:52steps in the same river twice.
51:54The river changes and Cancer Research.
51:56We had passed thresholds
51:57as compared with 1971.
51:58We now have a molecular
52:00understanding of these diseases,
52:01and we're ready to take
52:02a crack at this again.
52:03I I've been trying to make this point
52:05in it for awhile now and I I found it
52:07actually a really good analogy that
52:08I like a lot in an excellent book on
52:10the history of the National Cancer
52:11Act by Abby Glucan and Charlie Fuchs,
52:14both of Yale.
52:15Entitled a new deal for cancer,
52:17it makes a point that I've long believed.
52:19It points out that the optimism for
52:21so many of the players held for the
52:23rapid cure in 1971, for example,
52:25Sidney Farber said he thought a cure
52:27for cancer could be achieved by 1976.
52:28But as the book notes,
52:30the foundational understands if cancer
52:31hadn't really been grasped in 1971,
52:33and so there's this quote from
52:35Sol Spiegelman,
52:35who is director of Columbia's
52:37Institute for Cancer Research,
52:38that I really like,
52:39which says an all out effort at this
52:41time would be like trying to land a moon,
52:42a man on the moon without
52:44knowing Newtons laws of gravity.
52:4650 years Now later we know what we
52:48don't know, and that's what's changed,
52:50and we know how we're going to
52:51end cancer as we know it,
52:52when before we really didn't
52:55know that next slide.
52:56So whatever progress or whatever
52:58successes in certain that they will
52:59be possible only because of the work
53:01of the last 50 years and it really
53:03build on the work of individuals like
53:05Paul Calabrese and the legislation
53:06that enabled so much of his work,
53:08I suspect that those of us who
53:10worked so hard to get President Nixon
53:13signature in 1971 might have been
53:14disappointed to know that a half
53:16century later we're still losing
53:18600,000 Americans each year to cancer,
53:20but I hope they would have been.
53:21They would be gratified to learn
53:23that despite the fact that the
53:24problems turned out to be so much
53:26more complex than we ever imagined.
53:27The passion, inspiration,
53:29dedication of the generations
53:30that followed have
53:32led to astounding progress nonetheless.
53:34So thank you for the opportunity
53:35to speak today and thank you
53:36for the opportunity back to you.
53:41Uh, thanks Dad, that was
53:43wonderful and I I think,
53:44uh, Paul is probably watching from a high
53:47and I'm very happy to see all the progress.
53:49It's our tradition at the Calabrese
53:51lecture to ask his brother
53:53Guido to ask the first question
53:55and I see Windows on in Italy.
53:57Guido, can you hear me?
54:02Unmute start Finder here I am.
54:05I'm in Italy and I was delighted.
54:07Can you see me and can you hear me can?
54:12I was delighted with the lecture because
54:1550 years ago Paul said to me but the aim.
54:20Was realistically not to end cancer,
54:25but to get so that a cancer diagnosis was
54:28no different from a diagnosis of high
54:31blood pressure or of cardiac problems,
54:34so that somebody might live for the
54:38longest time or shortest of time,
54:41but that cancer was not a death
54:43sentence but was a life sentence
54:46to be dealt with decently and well,
54:48and this lecture.
54:50Was so much in that line,
54:53but it made me smile because that's
54:55what Paul was about.
54:57But there's something else in this
55:00lecture which really struck me and
55:03that was the continuing difference
55:05even when there are diagnosis of it
55:09at the same time in results among
55:12people because of race because of
55:14poverty because of all the things that
55:18have cursed us in America over so.
55:21Long and I just wonder how much
55:24the fact that monies are being
55:26given to cancer as they should,
55:29because cancer is such a dramatic
55:33disease in people's mind.
55:35How much this can be used not only
55:39to diminish these differences
55:41in cancer treatment,
55:43but in treatment of diseases generally.
55:46That is, using what is needed to make cancer.
55:51Treatment more equal to different
55:54people based on race and poverty
55:58so that all medical treatment
56:01becomes more equal in this country.
56:04Thank you.
56:07Yeah, well, thank you,
56:08Judge Calabrese T and it's a very
56:10important question and I think a really
56:13important point to make is that.
56:15You know, addressing the things that Dr.
56:16Disparities in health outcomes,
56:18United States will not just
56:19benefit patients with cancer.
56:21They would benefit you know, presumably,
56:22and we actually have very strong
56:24evidence that they would benefit.
56:26You know individuals for lots of
56:28diseases and and would improve health
56:30in in many ways for the public.
56:33So think about something
56:34like tobacco control,
56:35which is really been quite
56:37successful in certain population,
56:38United States and not so successful
56:40in other populations intend to
56:42correlate with continued combustible
56:44use of combustible tobacco.
56:45Correlate with low socionomic
56:47status and and less education.
56:49And you know if we could reach those pockets,
56:52the benefits of the backer control
56:54would be way beyond cancer.
56:56They would they would go to many
56:57other diseases and general health,
56:59so it's it's a really important
57:01question and we think that the.
57:03And through the last, you know,
57:05I'd say 20 years the NCIS become
57:07very interested in this topic of
57:10dissemination and implementation.
57:11Science is like when you know
57:13something works.
57:13It works just fine at the tertiary cancer.
57:17Excellent,
57:17outstanding academic hospital,
57:18but then it doesn't translate
57:20out in the community.
57:21What happened there?
57:22Why doesn't that work and where
57:24is the where do things breakdown?
57:25Obviously many of these things
57:28are are ascribable to things
57:30that we we know a lot about.
57:32You know the fractured nature of US.
57:33Healthcare, you know,
57:35inequities in education.
57:36For example, you know states,
57:38but I'm also I'm struck by how
57:39often a disparities are often
57:41driven by things that we didn't
57:42appreciate as being so important.
57:44You know, for example,
57:45a study in in,
57:46in in,
57:47disparities in ER positive breast
57:50cancer by race showed that a large
57:51part of this theory was driven by
57:53adherence to therapy of the medicine.
57:54So it was really the ability to
57:56continue taking medicine because of
57:57costs of the medicine are presumably
57:58the hassle of going the pharmacy.
57:59So you know,
58:00I think we had lots of reasons in
58:01our mind why that disparity existed.
58:03But, you know, one of the main.
58:04Drivers was really something
58:05so narrow and addressable,
58:07so that's why I think this this line
58:09of research is is really important.
58:11Obviously the NCI with its mirror
58:12on the order of $7 billion a year
58:15budget can't fix care and education.
58:17United States those are much bigger problems,
58:19but I think we can do the foundational
58:21science that explains what's
58:22really driving these inequities.
58:25Thanks Dad, as Stephen Calabresi
58:27has a question. Uh, thank you Doctor
58:29Sharpless for that presentation.
58:31It was really wonderful.
58:32There may be an easy answer
58:34to this question, but I was
58:36curious given the recent
58:38advances in immunotherapy and treating
58:41cancer, and given the remarkable
58:43such success of the MI RNA vaccines,
58:47that Moderna and
58:48Pfizer developed against
58:49COVID, is there more work
58:51to be done on vaccination to prevent cancer?
58:56And is that a field that is potentially?
58:59Worth looking into in the future.
59:02Yes no. I think that UM.
59:05Near the M RNA platform is very exciting
59:08and particularly for the potential
59:09of sort of what are called bespoke,
59:11you know totally personalized
59:13medicines and certainly an area.
59:14We've been thinking a lot about Moderna.
59:17I think you're probably aware
59:18started out as a cancer company.
59:19I mean some of their initial products
59:21were were targeting cancer and and and I
59:23think pivoted for a variety of reasons.
59:24Related technology to vaccines but
59:26still has an interesting cancer and
59:28it's still supporting a clinical
59:30trials and cancer patients and
59:31and so I think that this approach
59:34makes a lot of sense in the area.
59:35Of personalized vaccines,
59:37but maybe maybe other areas as well.
59:39I can tell you that I I have one concern
59:41about it that we don't talk about very much,
59:43but I think we're probably
59:44talking about more,
59:45which is that you know,
59:45having spent time at FDA,
59:47the regulatory pathway for bespoke
59:49medicines is entirely unclear to me.
59:51It is not certain how you would take
59:54medicine that you intend to use in one
59:56individual and make that into an FDA
59:59approved product under current law.
60:00And I think that and and.
01:00:02And frankly,
01:00:02I know this is a big turnoff to many
01:00:04of the industry partners in this.
01:00:06Face who are worried about how
01:00:07they would make a viable product.
01:00:09Even if you could use it in thousands
01:00:10of cancer patients if the product
01:00:12is different in each patient is
01:00:13different molecule in each patient.
01:00:15You know?
01:00:15How is that going to work from
01:00:16regulatory framework?
01:00:17So I think we need some clarity
01:00:18on this topic.
01:00:19I think the you know the FDA.
01:00:22It needs to provide further
01:00:23guidance on bespoke products and
01:00:25and perhaps we even need legislators
01:00:26to write new law in this area,
01:00:28but it's really exciting
01:00:29and it goes beyond cancer.
01:00:31By the way, there are many,
01:00:32many rare diseases,
01:00:33particularly disease of children,
01:00:34where these highly personalized
01:00:35medicines could be valuable as well.
01:00:37So I think as a society it's really pressing.
01:00:38We figure this
01:00:39out great. Well, let's say we're at the hour,
01:00:41but we have one special guest.
01:00:43And before I do that,
01:00:44I just want to remind the fellows
01:00:45that we have a half an hour virtual
01:00:47lunch with Doctor Sharp list.
01:00:48So please stay on this very line,
01:00:50but I'm really excited.
01:00:51Eric Weiner. Are you on?
01:00:52So Eric is our new director and
01:00:54actually he gave the Calabresi
01:00:56lecture about 8-9 years ago and Eric,
01:00:59I just love for you to say a few words.
01:01:01If you have time.
01:01:06I think we we missed our window.
01:01:09Well, yeah. That's OK,
01:01:12so Eric was a Calabrese lecture.
01:01:15Very happy that he was here today and
01:01:17he heard that he heard your talk net
01:01:19and I'm sure you have business with
01:01:21him in the not too distant future.
01:01:22Yeah, I know I I, you know I I've
01:01:25known Erica while given the Boston
01:01:26connection and I think what, what,
01:01:27what a great development in turn of
01:01:29events to see him assume a leadership
01:01:31role at Yale and at the NCI we look
01:01:33very forward to working with her right?
01:01:35Well listen this has been
01:01:37absolutely fantastic.
01:01:37We had one of our largest turnouts
01:01:40for grand rounds in the virtual era.
01:01:42And what we're gonna do now
01:01:43is I'm gonna thank you, Ned.
01:01:45And thank you Vince.
01:01:47And then it's gonna stay on
01:01:47with me with the fellows.