At a Glance: NCI’s Division of Cancer Prevention

September 15, 2021

Information

Yale Cancer Center Grand Rounds | September 14, 2021

Dr. Philip Castle

ID6903

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00:00Hey everybody, I'm Kerry Gross
00:02director about cancer outcomes.
00:04Copper Center and also primary care doc.
00:08And with that background,
00:10it's a particular treat to welcome
00:13Doctor Philip Castle to join us today.
00:16Doctor Cassell's work has been
00:19foundational in our understanding of
00:21the etiology and prevention of HPV,
00:24associated cancers and cancer prevention
00:26with General Electric Castle received
00:29his PhD in Biophysics, actually.
00:31A masters in public health
00:33from Johns Hopkins,
00:35who was previously the Chief
00:37scientific officer at the American
00:40Society for Clinical Pathology.
00:42There's been a principal investigator for
00:44more than 15 years of self initiating,
00:46conducting and reading by several
00:49large NCI sponsored electoral
00:52and clinical research studies,
00:54both in the US and abroad.
00:56Is that the party is widely appreciated.
00:59It's contributed to virtually every
01:01major guidelines regarding regarding at
01:04cervical cancer screening and prevention,
01:06and his work really has extended globally.
01:09His papers have been cited more
01:11than 40,000 times in aggregate.
01:13Currently Dot the castle serves as the
01:16director of the Division of Cancer
01:18Prevention and Control at the NCI.
01:21Working overseas.
01:21The conduct and support our
01:23research in cancer prevention,
01:25early detection and screening.
01:28And now is a particularly
01:31relevant and timely setting for
01:33Doctor Castle to present to us.
01:35This is the 50th anniversary
01:37of the National Cancer Act,
01:39and as we reflect on the role of
01:42science in public health and society
01:44in general and in the efforts
01:47against cancer in particular,
01:49the role of prevention is a means
01:51to decrease the burden of cancer.
01:53This clearly is central work,
01:55so thank you for joining us today.
01:57Doctor castle.
01:58And we look forward to your comments.
02:01Thank you so very much.
02:02It's a real honor to be here and
02:04it's a real honor to lead the NCIS
02:07division of cancer prevention.
02:08Today I'm going to give you sort
02:10of a broad overview,
02:12recognizing as I learned that many of
02:14my colleagues don't actually understand
02:16what the division of cancer prevention does,
02:18how it's different from the other divisions,
02:21but also to.
02:23Highlight the work that we
02:25support and to engage you,
02:27hopefully in the future.
02:28In in some of these cancer
02:31prevention activities.
02:33So just a few disclaimers that get started,
02:36opinions expressed or mine should
02:38not be interpreted as representing
02:40official viewpoints of EU.
02:42S.
02:42Department of Health and Human Services,
02:44the National Institutes of Health,
02:45the National Cancer Institute,
02:47or the Division of Cancer Prevention.
02:50My comments are informal and should not be
02:52taken as a signal for funding priorities.
02:54I will speak in broad terms
02:55of what I think is important,
02:57where I would like to see the science
02:59of cancer prevention head towards
03:00in the future and my aspirations,
03:02whether and when I or we can
03:05implement those priorities depends
03:06on many factors beyond my control.
03:09I wish that weren't the case,
03:10but it is in fact the case I wanted
03:13to highlight the burden of cancer
03:14and I know you all know this,
03:16but it's it's.
03:17It's the starting point for this discussion
03:20or any discussion about prevention.
03:23Which sometimes I think UM, sort of
03:26gets put into the second row here, but.
03:30As you can see in the slide here on the
03:33in the left panel is the expenditures
03:36per billions of dollars annually for not
03:39seeing your slides, we need to share.
03:43See what's going on here, sorry.
03:59My apologies, can you see that now?
04:03Perfect thank you.
04:04OK so in the left panel is
04:07by cancer expenditures and
04:09billions of dollars annually.
04:11And then for the most common cancers
04:13are the most lethal cancers you
04:15can see that it's not billions,
04:16but it's tens of billions of dollars,
04:19and in fact the national costs of
04:21cancer were estimated to be 190 billion
04:23in 2015 and now 209 billion in 2020,
04:27an increase of 10% over that period of time.
04:30And that doesn't really even account
04:32for the hidden costs of cancer,
04:34which is a product approximated
04:36to be 100 billion.
04:37And as I'll show you the next slide,
04:40we've made a lot of advances.
04:41Certainly in the treatment of cancer.
04:43But we still have 1.5 million cancers
04:46and .6 million related deaths every year.
04:49And just to give you a perspective and
04:52on that as bad as COVID was and is a
04:57point 6 million deaths is almost two full.
05:02Not quite,
05:03but almost twofold more deaths than
05:05those than that caused by COVID.
05:08So, uh,
05:09what what's happened over the last 45 years?
05:13You can see that arguably,
05:16I'm here are there's a CDC data
05:18rate per 100,000 of the population.
05:20We've really not made any significant
05:23headway in the incidence of
05:26cancer in males and females.
05:28There's a sort of a peak
05:30in males in the early 90s,
05:31and that's come back down,
05:32but it's about the same level as it was in
05:361975 and in females it's gone up slightly.
05:40I mean partly in dude and
05:42aging population to be sure.
05:43But you know, these are not the
05:45kinds of numbers we'd like to see.
05:47Certainly we've made some advances
05:50in the management of cancer.
05:52In survival,
05:53particularly well in both in both sexes,
05:57maybe perhaps more in males than females,
06:00but I would say also here that even
06:04preventing cancer related death.
06:06It's a long life or longer life of
06:11significant morbidity and lower
06:13quality of life to live with cancer,
06:17as I know from my own family members.
06:20So the mission of the division of
06:23Cancer prevention is as follows.
06:25The NCI Division of Cancer Prevention.
06:28Lead supports and promotes
06:30rigorous innovative research and
06:32training to reduce risk burdens.
06:34Consequences of cancer to improve
06:36the health of all people,
06:37and you'll understand this a little
06:39better as I go through and give
06:41you a this at a glance of view of
06:44the division of cancer prevention.
06:45Uh,
06:46just to highlight that I almost do nothing,
06:48this everything that you're going
06:50to hear about it has to do with
06:52an amazing staff.
06:53Uhm,
06:54shown here we have groups focused on
06:58method more methodologic approaches
07:00or exposures and we also have organ
07:04specific areas of research as well.
07:06I will highlight some of these,
07:08but that is not to say that there
07:09I mean we could talk for hours
07:11about what everybody is doing.
07:15Uh, I put up this translational continuum,
07:17and again, you'll see why here in a
07:19moment to really sort of highlight this,
07:22the stepwise development of interventions
07:25and and, and therefore where we fit into
07:28that from basic science to translation
07:30to humans translation to patients,
07:32translation to practice and translation
07:35in their community. Showing up.
07:37This in terms of the divisions
07:39and these are approximations.
07:41I wouldn't say that any one of of
07:44these you know nobody's limited
07:46perception completely to this area,
07:49but I would say 90 to 95% of the work.
07:52Each of the division is sort of
07:54represented here and in over with an
07:57overlay of the translational continuum.
08:00We really focus on the.
08:03An innovation to prevent cancer
08:06and to manage symptoms.
08:08As I would talk about later
08:10and try to you know.
08:11So we identify and we do early
08:13validation work with the hopes that
08:15successful strategies then get more
08:17or less handed off to the division of
08:20Cancer Control and Population Sciences.
08:22So we really there really are two.
08:25Population science groups at the
08:27NCI were a little bit sort of.
08:30I would say the forgotten group or the
08:33the the other population science group.
08:36I think people are generally more
08:38familiar with cancer control
08:39and population sciences because
08:40it tends to dovetail more.
08:44More easily with the Cancer
08:46Center in the in those renewals,
08:48particularly related to.
08:51Uh, uh, outreach?
08:52Uh, we're actually probably more
08:54aligned in terms of the work we
08:56do with the division of cancer
08:58treatment and diagnosis, Albert.
09:01We spend a lot more.
09:03We invest a lot more in
09:05treatment and diagnosis.
09:06We work closely with the
09:07division of Cancer Biology,
09:09particularly on identifying pathways
09:11for cancer or carcinogenesis
09:12that can be then translated into
09:15prevention strategies and then
09:17the intramural program with the
09:19center of Cancer Research and
09:21division of cancer epigenetics,
09:23which we're increasingly working
09:25closely with to try to get
09:28their innovations into clinical
09:30practice and into public health.
09:33So and you all know this,
09:35but it's always useful to
09:37sort of declare these things.
09:40Cancer prevention is really, really hard.
09:43There's certainly an event
09:44bias or what I call an event by
09:47success is the absence of events,
09:48and therefore there are no champions.
09:50This is also referred to
09:52as the prevention paradox.
09:54Our first mission is to keep
09:56healthy people healthy.
09:56First do no harm,
09:58and I'd say this applies more to
10:01public health and even medicine,
10:03and I point out that you know when
10:05we do screening people think of
10:06screening as a one step process,
10:08but it's really a two step process.
10:10The first step in screening is
10:12to tell healthy people there.
10:13Healthy and they don't need to
10:15be screened again for whatever
10:16is an acceptable interval.
10:18And then among the positives
10:19we we try to rule in.
10:21Who needs immediate care.
10:23But it's also important to
10:25remember in the general population,
10:27most people at any one time will not be.
10:30Uh, you know,
10:31will not get cancer or particular
10:33cancer so 49 out of 50 women would never
10:36get cervical cancer if we did nothing of all.
10:38We didn't screen them.
10:39We didn't vaccinate them,
10:41etc etc.
10:41It's a high bar because of the rare
10:44events and the relatively small benefits,
10:47and there's very little tolerance
10:49for toxicity and and then the final
10:52barrier if you will, is there.
10:53I think there's a perception that
10:55there's no money in prevention and I
10:57I would challenge that only to say that.
11:00Nobody wants to get cancer,
11:01and so there's a lot of people out
11:03there that don't want to get cancer.
11:04I mean, uh, you know,
11:06so that I think that there's actually,
11:08you know, given the big denominator,
11:09there's a big opportunity for industry
11:12to get involved in and prevention.
11:14I think that what scares them off is
11:17the the the expense and difficulties
11:21of doing large trials to demonstrate.
11:24Efficacy and effectiveness and the very
11:28low tolerance for toxicity or adverse events.
11:32This is highlights sort of the
11:34causes of cancer and where they are.
11:36Some of the opportunities are.
11:37I wouldn't say that there it's comprehensive.
11:40This is from Scott Lippman in it at all.
11:43Obviously obesity is and tobacco or
11:47the main causes of cancer tobacco,
11:53you know,
11:53we we even do some work in this
11:56area, particularly for
11:57anti nicotine approaches.
11:59Obesity I think hangs over all of us in
12:02terms of how do we tackle this problem?
12:05How do we mitigate the effects of BC?
12:07What is the you know?
12:09What is the causal relationship
12:10of obesity with cancer?
12:12Is it inflammation?
12:13What kind of inflammation? Etc etc.
12:15And then a variety of other causes.
12:19Viruses are near and dear to my heart
12:21because of my work on human papilloma virus,
12:23which causes 5% of of cancers globally,
12:29so it's. And HPV been my training ground on.
12:34I started off as a lab scientist but
12:37moved into molecular epidemiology
12:3820 years ago and continue to learn
12:41from the study of HPV in many ways.
12:46So if we think about this causal model
12:50where we go from normal to initiate it
12:52to precursor States and invasive cancer,
12:54it really helps us sort of identify
12:56the roles of different groups.
12:58But also where we where the opportunities
13:00are for intervention now precursor states,
13:03I mean those are somewhat artificial
13:05slices of the of the pathway,
13:07and in case of cervical cancer that
13:10probably really aren't distinct states,
13:12just clinical diagnosis that fall
13:15within this area somewhere between.
13:17Initiated and pre cancer.
13:22So what can we do right now?
13:24Obviously and and I will say highlight
13:27that I recently published an OP Ed
13:29in Stat to talk about really these
13:32same strategies that are being used
13:34for COVID can be used for cancer
13:37prevention and that we really need a
13:39pandemic response for cancer prevention
13:41because of the annual burden of cancer.
13:44So avoidance is one strategy or
13:47primary prevention if you will,
13:50through tobacco prevention, HPV and HB.
13:54HPV vaccination treatment of
13:57H pylori potentially.
13:59And then sex sort of secondary
14:02prevention through tobacco cessation,
14:03screening and diagnosis.
14:05And those tools, avoidance vaccinations,
14:08bringing treatment,
14:09or the very things that we're
14:12using now to battle COVID.
14:13And really we need to highlight
14:16those and bring them back into
14:19the prevention discussion.
14:20Uh, we're working more and more in
14:22the area of interception of cancer and
14:24we'll talk more about this in moment,
14:26right?
14:26And this is sort of moving us
14:28towards what people refer to
14:30as precision cancer prevention,
14:32and I'll talk about that a couple
14:34times through this and even propose
14:36a broader definition of precision
14:39cancer prevention.
14:40But obviously,
14:41tamoxifen and its derivatives
14:42for breast cancer for those who
14:45are at high risk and seats for
14:47colon cancer immune modulators.
14:49Drugs that target oncogenic drivers and
14:52re activators of tumor suppressor genes,
14:55for example.
14:58So I'm going to present this
15:01this chart or this picture for
15:04our three main programs here.
15:06It's what I call our
15:08preventive agent R&D pipeline.
15:09And the thing that I want to
15:11point out is that people don't
15:13always recognize these programs,
15:14particularly in DCP.
15:15We gave a presentation for this
15:17new program called Capital,
15:19which I'll explain in a moment
15:22to the BSA members.
15:23The NCI Board of Scientific advisors.
15:27And one of the members didn't
15:28even know what prevented.
15:29So let me so I'm going to drag
15:31you through this because I want
15:33to engage you in the process of
15:35developing new prevention strategies.
15:37So cap it is a new program.
15:39It's a targeted agent identification
15:43program for preventive agents.
15:45Prevent is our preclinical development
15:48and validation program and even you know,
15:51to the extent of producing GMP grade
15:54drug for trials seek Tenet is our early
15:58stage clinical trials network and then core,
16:02which I'm sure everybody's heard of, is our.
16:04You know,
16:05our big clinical trials network.
16:07For primarily for phase three trials like T.
16:10Mist.
16:12We had a moon shot consortium
16:14on come on novel advents.
16:16You lack net is to look at prevention of
16:20HPV related disease in HIV and people
16:23living with HIV in Latin America.
16:25We have funding opportunities for cancer
16:28prevention and control trials and a new
16:31one hitting the street on in yellow.
16:33Here,
16:33cancer trials,
16:35planning and feasibility.
16:36It's kind of like a P20 funding opportunity.
16:39I can't remember what the the mechanism is.
16:42But the the basic idea is that these trials
16:45are very hard to do and to do denovo,
16:48and that if we spent some money investing in,
16:51we would.
16:53You know, get the get the planning done
16:57in the and test the feasibility before
17:00they came for an R1 level funding.
17:03Precision Cancer Prevention
17:04centers is is is the future.
17:07I hope it's my dream and fantasy
17:09that it would and it would
17:11dovetail with this R&D pipeline.
17:12But basically two engaged centers to kind of
17:18create their own pipeline that would move.
17:23Move from discovery to early
17:26translation to early human trials and.
17:29I emphasize here as shown below that
17:33although these programs sit at the NCI,
17:36they're open for investigator initiated
17:39research to take advantage of these programs,
17:42and we encourage it.
17:43We want you to come forward
17:45with new prevention strategies,
17:47and again I want to emphasize that
17:49what DCP focuses on innovation,
17:51new strategies that we haven't
17:53that you know are not.
17:55You know that need development
17:58and early validation.
18:01This just shows the CPCT net,
18:04which is really this early phase clinical
18:08trials group that's across the country.
18:11With data monitoring and uhm, uhm?
18:15A board that's a data management and
18:20that coordinates these activities,
18:23optimizes clinical trial designs,
18:25developed surrogate and
18:27intermediate endpoint biomarkers,
18:28test novel imaging technologies,
18:30and develop further insights into the
18:34mechanisms of cancer prevention by agents.
18:37And this is led by even zabbo.
18:41Here's a couple of the approved
18:43trials that are already underway,
18:45one on NAFLD,
18:47a HPV vaccine delayed booster trial.
18:52Uhm and prostate uhm.
18:54A management trial as well.
19:00These are some of the.
19:03Protocols that are under development
19:05a wide range from breast cancer to
19:09FAPA metformin as a chemopreventive
19:11agent for lung cancer and
19:13high risk of these patients.
19:15I'm not going to read through all these.
19:17You can have these slides and
19:19kind of see the the breadth and
19:22depth of the trials at the NCI.
19:26We're doing a number of studies
19:29on topical tamoxifen to look at
19:32whether we can sort of change
19:34the benefits to harms ratio,
19:36and I'll I'll come back to that point.
19:39By delivering tamox into that issue at risk,
19:42and in this case breast cancer.
19:44Looking at some biomarkers
19:47in DCIS breast density.
19:49Measuring inter individual variation
19:54and looking at serum and tissue
19:57concentrations of of of the
20:00drug being delivered topically.
20:06Are you lacnet which I mentioned before?
20:08Is our HPV prevention clinical trials
20:11network in Latin American Caribbean,
20:14and there are three consortium members
20:17working on a variety wide variety of
20:20interventions from some vaccination
20:22work to screening to pre cancer
20:25therapeutics and people living with HIV.
20:31So then that leads us into discussions
20:33of screening early detection,
20:35which we've done a lot.
20:36Obviously, Plco is one of the major U S
20:39trials that was sponsored by the Division
20:42of Cancer Prevention and here above,
20:45here in the yellow.
20:46I just wanted to state that we are
20:48more and more thinking about what
20:50I call risk informed screening,
20:52so using risk to decide who and when
20:54people need to be screened or to modify
20:57the management of the screen positives.
21:00And it also provides a possible
21:02or potential for intervention with
21:04targeted preventive agents if we know
21:07the biology of what that risk is,
21:09then we could then combine both screening
21:13strategy with a preventive agent strategy.
21:17So this is our screening early detection
21:20R&D pipeline at the core of this is Dern,
21:23which has been just renewed and is
21:27now 20 years in the making or in its
21:30in its in its life and it continues.
21:34I will present a few slides on that,
21:36but we have some related projects
21:39around pancreas cancer, PCDC,
21:41liver cancer, TLC,
21:42L we have a liquid biopsy consortium
21:45and we have an image ingane.
21:48Biomarkers consortium T bells and
21:50new program to help us differentiate
21:53between indolent and aggressive cancer.
21:57I'm sure many of you have heard
21:59of H Tan which is the human tumor
22:01Atlas network and we built off of
22:03that a pilot study called the Pre
22:06Cancer Atlas which we're hoping to
22:08renew in the subsequent year or so.
22:11Uh.
22:12One of the big gaps that we need to fill is
22:15a screening and early detection network.
22:17Not that Encor doesn't do some of that,
22:20but.
22:20We really need to engage the primary
22:23care providers to recruit average
22:25risk populations into our trials,
22:28and so that's why I showed that in purple.
22:30We're developing a new lung
22:34cancer image library for improved
22:37interpretation of those images I
22:40mentioned you lacnet several times
22:42were now have on the street at Cascade,
22:45which is a another consortium
22:48to look at best practices for.
22:51Screening women living with
22:53HIV for cervical cancer.
22:56How best to screen them?
22:57Manage them and treat them.
23:00Last Mile is a project that
23:02I'm Co leading on getting self
23:05collection and HPV testing approved.
23:08For routine screening in the
23:10United States and so forth.
23:14Uh,
23:14we're hoping to stand up some risk
23:17informed screening for cancer trials,
23:19or what I call risk trials,
23:21and we have a large trans NCI liquid biopsy,
23:25multi cancer early detection
23:27program that I've initiated and
23:29we will be working on that,
23:30including what I hope is a large
23:33platform trial to look at some of
23:35these technologies going forward.
23:37This just gives you a sense of end
23:40core which is involved in all of
23:42those activities that preventive
23:44agent development program as well
23:46as the screening early detection.
23:48There are over 1000 clinical sites,
23:5146 centers and affiliates and
23:53more than 4000 investigators.
23:55This is led by Warden Mckaskle
23:58Stevenson who's doing an
23:59incredible job of.
24:01Herding the cats if you will.
24:03Uh, I'm sure you've heard of a team nest,
24:06which is a randomized clinical trial
24:09to compare 2D versus 3D mammography.
24:12I'll show you some of the not results,
24:15but there are recruitment in our
24:18recruitment struggles during COVID.
24:19We've just launched Forte,
24:21which is to look at best
24:24rap best management of.
24:26You know low, fairly low risk.
24:30Populations who have wanted
24:31two non advanced polyps.
24:33And then a management trial
24:37for pancreatic cysts.
24:41You can see here the team missed was,
24:44as was many of our activities adversely
24:48affected by the COVID pandemic,
24:51shown here highlighted down here,
24:53you can see that the enrollment almost went
24:56to zero during the height of the pandemic.
25:00It's now come back and exceeded
25:03the monthly recruitment levels.
25:04So we're very excited about that and
25:07over time will start getting some
25:09readouts from the trial itself on.
25:113D versus 2D mammography.
25:15Uhm, this just highlights the cascade,
25:18which is a global multicenter
25:21cooperative agreement.
25:22Clinical trials network.
25:23To optimize this cervical cancer
25:25screening and treatment cascade
25:27for women living with HIV.
25:29Looking at all these issues in
25:31the care continuum care of care.
25:34From screening uptake to management
25:36of positives,
25:37pre cancer treatment and so forth.
25:40Although this will be a will
25:42have sites in the United States,
25:44we will also include sites in
25:46low and middle income countries.
25:50A last mile, as I mentioned,
25:52is really going to, we hope,
25:55bring HPV testing of self collected
25:58samples online in the United
26:00States and we're working very
26:02closely with the FDA on this.
26:04And just to say that.
26:06I've spent 15 years working on
26:09this topic more than 15 years.
26:11I know I look young,
26:12but it has been more than 15 years
26:15working on this particular one,
26:17that the idea that we can democratize
26:20screening by bringing screening to
26:23the homes or to convenient areas for
26:27participation in screening, I think,
26:29is going to be a game changer,
26:32not just nationally but globally.
26:34Although most countries don't
26:36necessarily take FDA approval.
26:38Directly in consideration,
26:39it is a big deal to have an FDA approval
26:43for a particular intervention so.
26:46We're very excited about this initiative,
26:49which we're hoping to launch
26:51in the next year or so.
26:53And and the other thing to say about
26:56this is from the meta analysis that
26:58I've participated in and others
27:00we know that women prefer this.
27:02I mean,
27:03it's kind of a no brainer and
27:05using a PCR based HPV test there's
27:08really little or no decrement
27:10in clinical performance,
27:12so this is a big deal.
27:14If we can get it underway.
27:15And it's a big deal in the global
27:19battle against cervical cancer.
27:24ERN was established in 2000, UM,
27:28to support investigator initiated
27:29research for the development
27:31and validation of biomarkers,
27:32foster interaction cooperation
27:34between academic, clinical,
27:36industrial partners or leaders.
27:40Furnish and apply standardized biomarker
27:42validation criterion quality assurance
27:44and facilitate regulatory process to bring
27:47biomarkers rapidly into clinical use.
27:49This is really our core
27:51biomarker for you know,
27:53screening for prevention and early detection,
27:56and Sudhir has done an
27:58amazing job on this program.
28:01This just gives you a sense of the of
28:03the of the different components of this.
28:06There are four main research
28:07groups shown here.
28:08On the left there's a steering executive,
28:11committees that oversee and review
28:13the program on a regular basis.
28:17We have a consulting team and then
28:19earn because of its breadth and depth,
28:21is really started to come.
28:24You know, permeate all areas related to.
28:30Early detection biomarkers related to
28:32early detection and prevention projects.
28:35Collaborations with Japan, India,
28:38France.
28:40Uhm, we've gotten Co funding
28:42from a variety of organizations.
28:44As I mentioned,
28:45there are tangential collaborative groups
28:48that expand on particular areas of EDR,
28:51and many associate members,
28:54federal partners,
28:55and we engage directly with
28:58pharma biotech industry.
29:02These are just some of the
29:03tests and I won't go over them.
29:05Obviously the perhaps the
29:06one that you're you know.
29:09Hearing a lot about his cancer seek
29:11which is a multi cancer early detection
29:13which was supported by the DRN.
29:16But there are many more and with this
29:18next round of renewal we're really
29:20hoping to push more things to FDA
29:22approval and into clinical practice.
29:24And that's really going to be our
29:26metric going forward is how much
29:28of this gets into routine care?
29:32Uh, I sort of alluded to this before,
29:34but the idea that we could bring
29:36these two pipelines together
29:37one is biomarker discovery,
29:39as well as and as well as bringing
29:44a preventive agent into the mix
29:47and so that you could detect
29:48and mitigate cancer risk, but.
29:52As I will talk about later,
29:53I really want to expand what we call
29:56precision cancer prevention and I will
29:58talk about that a little bit later.
30:00We also do symptom management,
30:01which seems odd, but that's the way it is.
30:04And actually I'm very excited about this.
30:06I think there's tremendous
30:08opportunity to improve symptom
30:10management and supportive care.
30:12What's really important about this
30:13to me is that the prevention and
30:16treatment of symptoms from cancer
30:18cancer treatment really has a profound
30:20effect on the quality of life.
30:22Of patients,
30:23but also their ability to survive
30:25the cancer and cancer treatment
30:27if we can manage symptoms better.
30:29As you well know,
30:30many of you are oncologists.
30:32The clinical performance remains
30:33high and so patients really not only
30:36get their first line of treatment,
30:38they get their second and third
30:40line treatment and even treatments
30:41that haven't been invented today
30:43but will be tomorrow.
30:46So we have a very broad portfolio,
30:49big and broad portfolio and and
30:52in symptom management shown here.
30:56Uh, those are the number in the
30:58upper left hand panel is the
31:00number of grants per per year.
31:05Are we really the only group at the
31:07NCI that focuses on pain management?
31:10And much of these activities happen
31:13within our clinical trials network,
31:15now called Encor. It used to be sikap.
31:19So this is again the pipeline and I use
31:22this as a is a sort of a platform for
31:25thinking about where we want to go.
31:27We have a lot of. You know,
31:31activities in our clinical trials,
31:32but what's really lacking is an
31:34investment in the biology and genetics
31:36of symptoms and symptom management.
31:38What we'll call here is precision
31:40symptom management, or symptom science.
31:43Uh, and so we really.
31:45I'm hoping in the next couple years to make
31:47to get some NCI investment in this area.
31:50There's no reason for trial and error
31:53related to symptom management anymore
31:55than there is for cancer treatment itself.
31:58Uh, we've been doing a lot on, UM.
32:01Defining patient reported
32:03outcomes and standardizing them,
32:05which is important for a sort of a base
32:08for doing anything to improve symptom
32:11management if we can't measure the outcomes,
32:14then there's not much for us
32:16to do and not much.
32:18We can't show anything.
32:19So the this moon shot that tolerability
32:22consortium focused on analyzing,
32:24interpreting,
32:25clinician and patient adverse event
32:27data to better understand Taler ability.
32:30Doing so by creating a consortium to
32:33share analytic approaches and so let
32:36me conclude with a few slides here and
32:40then it will open up for questions.
32:42These are certain my informal,
32:44UM, unofficial priorities,
32:46really understanding biologic risk and
32:49using that to guide what we do for patients,
32:54but also population risk to
32:56decide who gets screened and how.
32:59How to screen,
33:00how to screen positives are
33:02managed and how to harmonize care.
33:04What I call equal risk equal
33:06care for equal risk,
33:08which is an idea that we had promulgated
33:10over 15 years ago in the cervix.
33:12World,
33:13as we saw that there were the all
33:15these new tools coming and there
33:16was going to be a great deal of
33:18heterogeneity in the population.
33:20Risk to their vaccination.
33:22We really needed a organizing principle here.
33:25Obesity, as I mentioned before.
33:29Causes so much of the burden of cancer
33:32and we really don't understand it.
33:35If we did,
33:36we could mitigate its effects.
33:37Obviously,
33:38changing lifestyle behavior would be ideal,
33:40but I think it's a real challenge to get
33:42people to change their their lifestyle
33:45behavior over a course of decades.
33:48And so I'm not saying that
33:49we shouldn't invest in that,
33:50but I'm saying complementary to that.
33:53We really should understand the
33:55pathways and how obesity contributes
33:58to carcinogenesis so that we can.
34:01Combine that with changes in
34:03lifestyle and behavior.
34:05I think I've said enough about precision,
34:07symptom, prevention,
34:09and management, but I you know,
34:11just to emphasize that I,
34:12I think we need to move away from
34:14the trial and error that often
34:16occurs in clinical management.
34:17That's not a criticism of
34:18the clinicians at all,
34:19it's just that we haven't.
34:21We haven't really taken this as seriously
34:23as we should in terms of bringing the
34:26same kind of focus on precision medicine
34:28to this area as we have in other areas.
34:31Health disparities I. I think there's
34:34a lot of opportunity for innovation.
34:37I mentioned self collection developing point
34:40of care testing like for HCV. You know,
34:43bring the bring the tests to the people,
34:45or bringing the intervention of
34:47the people rather than just relying
34:50on them to come to the clinic.
34:52I know that persistent reality is
34:54a major risk factor for cancer,
34:57and then we're being bombarded
34:59with new technologies,
35:00AI multi cancer, early detection,
35:02synthetic biomarkers, etc etc.
35:04We really the NCI plays a pivotal
35:06role in sort of getting out in front
35:08and figuring out what's good and
35:11what's not without bias without.
35:13And gender and and I think we need
35:15to do that more and more as these new
35:19technologies rollout faster and faster.
35:21Uhm, I wanna pose something that
35:24might be a little bit controversial,
35:27which is a broader definition
35:30of precision cancer prevention.
35:32To achieve equitable care for all.
35:35And the core principles here are the
35:37benefits to harms ratio and understanding.
35:39All causes of differences,
35:41not just biological,
35:43which informs how we can be more precise.
35:45So what we've typically figured
35:47on is the what,
35:48which is based on an understanding
35:50of carcinogenic processes.
35:51Target early changes via
35:53screening or interception,
35:55but I want to add The Who into this,
35:57which isn't always integrated into this,
35:59which is who's at risk and how much risk.
36:01And that really tells us, not just.
36:05What age but what kind of screen?
36:10To use or what kind of intervention
36:12to use and what's the follow-up care?
36:15Where a?
36:17Alternative delivery strategies,
36:19like I mentioned home based sample
36:22collection collection of testing,
36:23app based interventions and so forth
36:26and then how benefits and harms can be
36:29manipulated by alternative routes of
36:32administration like topical tamoxifen,
36:34maintaining effective doses more
36:36consistently through sustained release
36:39to reduce toxicity and perhaps even
36:42increase improve the benefits.
36:44The cancer prevention,
36:46benefits and even strategies.
36:47For immunization and we we often
36:50focus on active immunization,
36:52but sometimes you can't develop a good
36:54response or a sufficient response.
36:56So maybe we have to make antibodies
36:59like anti nicotine antibiotics
37:01which we are supporting right now
37:03to give people the immune spot
37:06immune response that they need.
37:08I think this is my final slide,
37:10which is just a call out for our
37:12cancer prevention fellowship program,
37:14from which I spawned.
37:15So how bad can it be?
37:18This is a multidisciplinary,
37:19diverse,
37:20and highly competitive postdoctoral
37:22training program that provides flexibility
37:24for fellows to generate and pursue
37:27original scientific ideas and structure,
37:29to develop competencies,
37:30support their future as leaders in the field.
37:34But I'm very proud of is we've
37:37got now cancer prevention fellows
37:39from Costa Rica and we are working
37:42towards the idea of having an ongoing
37:45international training component to
37:47this cancer prevention fellowship.
37:49And then the Cancer Prevention
37:52Fellowship program has alumni across
37:54all across the country in the world.
37:57You know it's been around for 35 years
38:00now and fellows are at major cancer
38:05centers and leadership positions.
38:07Government agencies, research firms,
38:09foundations, and policy organizations,
38:11and the website for the Cancer
38:13Prevention Fellowship program.
38:15Shown there at the bottom.
38:17So with that, I'll say thank you
38:19and I'll take any questions.
38:22From the audience and thanks again for
38:24the invitation to Yale Cancer Center.
38:29Thank you very much.
38:31Doctor Castle and Great talking,
38:32kind of a whirlwind overview.
38:36What's been going on with
38:38exciting preview of next steps?
38:42So I'll ask people to send questions
38:44via the chat button while we're waiting
38:46for some other questions that they
38:49had one just to get the ball rolling.
38:51So. In your position,
38:54the decisions need to be made
38:56with regarding prioritization of
38:58large scale efforts forward in
39:01overarching strategies at the center.
39:04Beneath that there are four
39:06tactical decisions which.
39:08Which plans to find out which teams he
39:11grants or program projects so for WhatsApp.
39:14So my question to you is how do
39:18you track success that how do you?
39:19How do you know five years from now
39:21whether you made the right decisions or that?
39:24Like if you imagine an alternate universe
39:25where you could have been focused,
39:27you know the center could have been
39:29focusing on completely different things
39:30are completely different strategies.
39:32They can have different outcomes, so I don't.
39:34I'm just curious how you think about
39:37how you know how to evaluate the
39:39progress of the centers making it both.
39:42So what's the time horizon is one of
39:44the metrics for evaluating success.
39:47Boy you've touched it.
39:47I mean you went right to the heart of it,
39:49right?
39:50Not just from a programmatic standpoint
39:51but from a prevention standpoint,
39:53because it often takes more than five
39:55years to show any of this stuff works,
39:57and I think.
39:58That is sort of one of the major
40:02barriers for researchers getting
40:04into the prevention field because.
40:08It's just hard, you know,
40:08even you know and and the more
40:10successful you are like for screening,
40:13even harder it is to do a prevention trial,
40:15right?
40:15'cause then you start extending screening
40:17intervals to the point where you
40:19can't even study it within an hour one.
40:22So I mean some of these things.
40:24You know,
40:25that's why we have to do things more,
40:26sort of directed by the NCI
40:28as a clinical trial,
40:30rather than just relying on our one.
40:32I know everybody wants to put
40:33all the money into the R1,
40:34but my calling is to come up with
40:36the best prevention strategies
40:38and sometimes it just doesn't fit
40:40within the the framework of an R1.
40:42There's no way that I can know in
40:44advance whether my guesses are good.
40:46And as you pointed out,
40:47I have to make guess I have to make informed.
40:50I hope. Informed guesses.
40:51About where we should put our energies.
40:55I think what I've been trying to impress
40:58upon my staff and through my staff to
41:01the extramural investigators we want to
41:03ground this in the best science possible,
41:06knowing that even that may not be good enough
41:08and and one of the challenges and we were,
41:10we have an ongoing workshop
41:13the last couple days is that.
41:16We rely particularly for
41:18preventive agents on mouse models.
41:20But there's a lot of issues
41:23with mouse models.
41:24You know?
41:24How well does it recapitulate human biology?
41:28How much can we rely on that?
41:30Because what happens,
41:31of course,
41:32is then we go to, you know,
41:35human trials based on those results.
41:37Even the phase one phase
41:39two trials are expensive.
41:41They take a long time and and
41:43don't have an efficacy readout.
41:45So let's say the toxicity is OK.
41:47Then you go into a five or
41:49seven or ten year trial.
41:51And only at the end there do you figure out,
41:54Oh my God, this doesn't work.
41:55We've just spent $100 million for something
41:58that's not going to help anybody.
42:00So it really is a challenge
42:01and I don't have a good answer.
42:03I would say that one of the.
42:05Ways forward is we really
42:07have to think hard about.
42:09Surrogate endpoints for cancer
42:11risk or cancer mortality.
42:13So screening trials are
42:15particularly challenging because
42:17right now the only thing that we,
42:19I think everybody can completely agree
42:21upon is if it reduces cancer mortality.
42:24It works,
42:25but stage shift doesn't
42:27necessarily translate,
42:28at least right now into benefit,
42:31and you can see the UK ovarian cancer
42:34screening trial is an example of that.
42:36Although I I believe.
42:38Eventually stage shift should
42:40translate into mortality benefit,
42:42but until we've shown you know,
42:45until that becomes a reliable.
42:47Sarah did endpoint,
42:49it doesn't.
42:50It's hard to then recommend
42:52something for general use,
42:53so are you know one of our challenges,
42:55whether it's and I've been
42:58challenging the nutritional science
43:00group within our that we can't
43:02go into this black box of like.
43:04Eat this we you know we can get people
43:06to do this and then we're going to
43:08go into a clinical trial to show you know,
43:10reduction of cancer incidence,
43:11which will take years and years
43:13and years and years to do.
43:14We need intermediate endpoints
43:16that we can rely on that at least.
43:20Push us in the right direction,
43:21right?
43:22The screen out the you know some of
43:24the things that aren't going to work.
43:27I do think that we have because of the
43:29time and the expense we're going to
43:31have to be more specific than sensitive.
43:34We can't chase after everything,
43:36so we have to place a sort of higher
43:38bar in this development process
43:40and and recognizing that we're
43:43going to miss some opportunities.
43:45But the the opportunity costs of
43:48chasing after our tail are really
43:51significant and and problematic.
43:53So there is no good solution.
43:55If you have one, please tell me because.
43:57You know, we talk about this all the time.
44:00It's just hard.
44:01It's hard to do prevention and
44:02yet everybody knows I mean.
44:05Even the most ******** oncologists
44:07would tell you no.
44:10You know,
44:10prevention is our first line of defense,
44:13and if you know and I always
44:15say this to my audiences,
44:16they walk down the street after Kovid
44:19when it's safe and ask the first
44:21hundred people you walk into and say,
44:23would you like your cancer
44:25prevented or treated?
44:27You know,
44:27I'll take that bet with odds that
44:29every one of them is going to say.
44:32Of course, I want my cancer prevented so.
44:35We all know it's important we
44:37all want it to go forward,
44:39but there are some real challenges to
44:40it and you know, as I mentioned before,
44:42the other challenge, of course,
44:44is very low tolerance for toxicity if
44:48you're primarily dealing with average risk.
44:50People who are on that day,
44:52most of them healthy.
44:53You can't. You know,
44:55you just can't do bad things to them,
44:56understandably so you know the the
44:59cervix world is sort of the outlier.
45:02In a way, it's it was the low
45:04hanging hanging fruit you have.
45:06You know you have relatively
45:08easily accessible tissue.
45:10You have a single causal agent.
45:13And you it takes 20 to 25 years ago
45:16from infection on average to cancer.
45:18I mean that you know,
45:20if we if I want to be honest about them,
45:22that one was supposed to be successful
45:24and and the other ones are much harder.
45:26So.
45:30Thank you, no, I don't have a clear answer.
45:32That's why I asked,
45:34you know, I, I believe me.
45:35If I had an answer I would share
45:37it with you, but I I don't.
45:38We struggle with this.
45:39I think the best thing we can do is brown.
45:41Listen better science, right?
45:43Understanding the molecular mean
45:44people wanted the magic bullet, right?
45:47If you eat this.
45:49This is going to work and I'm
45:50not saying that that won't work,
45:51but let's look at nutrition for a
45:53second here and I apologize to any
45:56nutritional epidemiologists or scientists.
46:00But the challenges of going
46:01from eating something into a
46:03clinical trial or profound right?
46:05So likely it's going to
46:07be a low penetrance thing.
46:09Even if you can measure it and the
46:11the ability to show it both at the
46:13lab level and if you go through the
46:16hill criteria and say we've got to get
46:18to a certain number of those before,
46:20we're going to go into a clinical trial.
46:21And then in most cases,
46:23you're really talking about a low
46:25penetrance or weak penetrance
46:27of or weak effect, right?
46:28So then you're talking about a huge trial.
46:31You know, you're really rolling the dice on,
46:34you know, 50 to $100 million trial
46:36to get the kinds of endpoints.
46:38And that's and we failed.
46:40We've had a number of failures
46:42and and you know,
46:43the other one that people have been
46:45chasing after his metformin and were or.
46:47And that's really turning out to not not
46:50be relevant in the prevention space,
46:52or it's so it's such a weak effect
46:54that we can't measure it, right?
46:55So that's the other problem.
46:56It might have a modifying effect,
46:59but we can't.
47:00Measure it and therefore we
47:01can't recommend it.
47:02And more importantly EU S Preventive
47:04Services Task Force can't recommend it.
47:06So and and you know that.
47:09So I mean part of it is we want
47:11something that's so cheap that
47:12you can get it off the shelf or.
47:13Or you can go to the grocery
47:15store and eat it.
47:17That has not panned out and and and
47:19there can be a lot of reasons for that.
47:22And it doesn't mean that it doesn't work,
47:24but it's hard to show it, and it's hard
47:26to invest that money in showing it.
47:29So follow up question thinking about
47:32the challenge of small effect sizes.
47:34Or it could be a large sample size
47:37of getting needed and create expense.
47:39Just thinking about the experience
47:41during COVID, but the UK.
47:44Some kind of ran circles around
47:46us as a nation with regard to the
47:48facility with conducting these large
47:50trials so that they have the recovery
47:53trial which actually enrolled 10%
47:55of all patients across the country
47:57who are hospitalized in the UK were
48:00involved in this large sent.
48:02You know, it's large,
48:04centrally coordinated trial randomization.
48:05It is generated a great deal of prompt.
48:09Really informative information is kind of.
48:11People have subsequently been
48:12saying or what can we learn?
48:14Post code it's not covered child.
48:16The more centralized approach,
48:17so you know building and and you
48:20mentioned is that the screening and
48:22early detection network and what
48:24are the strategies for creating
48:25this large amount of people.
48:27That and other things out there
48:28for large systems where we could
48:30be running multiple trials at the
48:32same time and have like a single
48:34infrastructure that's really, really big.
48:36Well we've,
48:37I mean to some extent we've done that
48:39with enkor, but that tends to be,
48:41you know,
48:42a cancer centers and you know
48:44oncology services.
48:44I mean,
48:45so some of the things that we're
48:46doing like Team Nest where you
48:47have to have radiology anyway,
48:49that that kind of works in that network, but.
48:52We have other networks that are
48:54in place that could be leveraged.
48:57It's a matter of coordinating
48:58them and being willing now.
49:00Some people would say Kaiser,
49:02though my experience and I've worked
49:04with Kaiser Permanente Northern
49:05California for 15 plus years.
49:07They're not really set up
49:08to do clinical trials,
49:10but one could imagine some combination
49:14of FQHC's and other providers,
49:17but starting to link them now.
49:20Between you and me,
49:21and I'll deny this if if anybody quotes me.
49:25If you start doing that,
49:26you start building a a public health.
49:28Infrastructure which I think
49:31COVID revealed we didn't have
49:33in the United States so.
49:35It is easier to do some of the stuff
49:37in Europe because they have organized
49:40programs they have organized health care.
49:42They have organized screening.
49:44We do not.
49:46But I think we can start pushing
49:47along those ways and it would be hope.
49:49My hope you know,
49:51probably long after I'm gone,
49:52but that by doing these kinds
49:54of activities where he showed
49:56networks can work together that
49:58you start to build the an informal
50:01organized screening program we know.
50:04There's a lot of data now to suggest
50:06that organized screening really
50:07makes a difference in terms of
50:09the effectiveness of the program,
50:11and I've had the privilege and
50:13just reviewing another paper
50:15from them of working with Norway
50:17for the last eight or nine years.
50:19And that's been a real pleasure to
50:21like what they can do to you know,
50:24and how they can make switches,
50:26how they can really get high coverage
50:29and and identify people for whom
50:31the system is not working right.
50:34And and come up with alternative strategies.
50:36So we know that screening like even
50:38for cervix we know that 2010 to 20%
50:41of people don't get their routine
50:43screening or don't get screened at all.
50:45And that's where half of the
50:47cervical cancers occur.
50:48So if we can bridge that gap,
50:50then we're making progress.
50:52So I mean, that's not the typical innovation
50:55that the division is focused on the past,
50:57but I'm a population scientist
50:58who's worked on some of this stuff,
51:00so that's why.
51:01I've sort of been thinking about my
51:04own definition of precision cancer
51:06prevention and trying to expand that
51:08to say it isn't just what we do like
51:12targeting carcinogenic pathways.
51:13It's also how we do it and where we do it,
51:16and for whom do we do it so?
51:22That's great baby. Let me pause, I do.
51:24I don't wanna turn this into a
51:26fireside chat would be nice I
51:27wanna try I like fireside chats.
51:29I'm happy to happen even separately.
51:31I can come back. Come.
51:35Well, I had one other question.
51:37No other questions from the groups.
51:38One other quick question is on.
51:41Mr. President.
51:43What are you thoughts about some form
51:45of a whole of government approach
51:47intersectoral approach were talking about?
51:50You know things like you know.
51:53Is it critical?
51:54So I wanted to find out which Ave,
51:56but you know we subsidized corn.
51:57So we our government on the one hand,
51:59is doing things that actually
52:01increasing the obesity our country.
52:02So just thinking are there
52:05avenues towards UM?
52:07Collaborating across sectors
52:09within the government,
52:10to, you know,
52:12think about changes at
52:13the policy level to come.
52:15I'm gonna change the diet or or you know,
52:19kind of incorporate.
52:21So we to evidence based policy change
52:23under some kind of demonstration.
52:25Part projects that could relate to things,
52:28which is the change in diet?
52:30You know population efforts to
52:31to address obesity or in see how
52:33that might affect cancer, right?
52:35Well,
52:36that's an interesting question of course.
52:39You know one of the things that
52:41I think about is, you know,
52:42this crossover of obesity and smoking.
52:44I mean,
52:45smoking suppresses diet,
52:46so is there going to be a point
52:48of crossover where where obesity
52:50becomes more important than smoking?
52:53But I'm not suggesting that anybody
52:55should start smoking to prevent recently,
52:57by the way.
53:00If you think about the successes of public
53:03health successes in the United States,
53:05they've really come.
53:07They've been driven.
53:09Sort of from the ground up, right?
53:11So if you look at smoking?
53:14You know it was lawsuits and you know,
53:16demands from the public to
53:18say this is this is, you know,
53:21we have to do something.
53:22Uh, even the you know one of the
53:24most successful public health
53:26campaigns has been HIV, right and?
53:29And and that's because.
53:32People demanded they got up on
53:34their soapbox and they said,
53:36you have to do something.
53:37And so I think you know one of my jobs.
53:40Although you know I'm not a implementation
53:43and dissemination person that's in DCCPS,
53:46but I've done that work for my entire career.
53:49And we can speak about the audit
53:51evening leading the division of
53:52cancer prevention if you want.
53:54But the I.
53:55I do think that we have to educate the
53:57public on the possibility of prevention,
53:59which is why I wrote that OP Ed to
54:01say if we can do this for COVID,
54:03we should be doing it for cancer prevention.
54:05That it's our first line of defense.
54:07Not that we're going to prevent all cancer.
54:09You know.
54:09I have no illusions of that,
54:11but I think there's a lot more and
54:12you have to make the investment.
54:14We invest three times just in the government.
54:17We invest three times more
54:18into treatment than we do.
54:19Prevention, let alone pharma.
54:21I mean pharma.
54:22It's got to be 20 to one or more,
54:26so I think it's it's getting.
54:30Getting voices to say.
54:31You know we need to make these
54:33investments in prevention.
54:35We need to understand obesity.
54:37We need to also have policies
54:40about you know what we make
54:43available for foods and and tax.
54:45You know one of the most
54:48effective strategies is taxation.
54:49So you know,
54:50I'm ten years ago I was sitting at
54:53the UN meeting on ends, you know,
54:55global warming CDs and you know,
54:56there's a lot of talk about the
54:59policy end and taxation, and you know,
55:03making sugary foods less available, right?
55:06If you want 'cause I think.
55:08This is my opinion and I I don't
55:11mean to be offensive in any way but.
55:13We are hardwired to eat.
55:16It is primal and I don't think we
55:18evolved to have unlimited access to food.
55:21But we do now.
55:22And so I know I have like no
55:25resistance and the fact that I'm
55:27sitting in home and I'm, you know,
55:30literally 20 feet away from
55:32my refrigerator is trouble.
55:34Like if I'm not around it,
55:35I'm much better off.
55:37I just am.
55:38But if and in fact, when I was at Einstein,
55:40I wouldn't take anything to work
55:41because I knew that, you know it just.
55:44If it's not there, I don't eat it,
55:46but if it's there,
55:47I will eat it.
55:47I have like no resistance and I
55:49don't think I'm unusual that way.
55:50I think I'm fairly represented
55:52despite my knowledge base,
55:53right? So I think you know.
55:56Our challenge is understanding
55:58fundamentally what we're hardwired to do.
56:01I mean, smoking is a little different
56:02because it's not a survival thing,
56:04but once you're addicted,
56:05you're addicted, right?
56:06Your wiring, you know, you've you've done.
56:09You've played.
56:10You know, it's haywire.
56:11You know you've messed with your,
56:13you know with the program.
56:15But food is fundamental.
56:17We eat to survive so.
56:19We evolved that capacity over,
56:22you know, millennia.
56:24To you know, and when we evolved it,
56:28we evolved it when we had to go
56:29out and hunt and gather, right?
56:31So there was a lot of exercise and
56:33the marginal difference between our
56:36caloric expenditure and our intake
56:39kept things in the right place.
56:40But now I can go down to
56:42the store and get you know,
56:44or to a restaurant and get 1000
56:47thousand calorie lunch easily.
56:49When we're not even supposed to exceed 2000,
56:52right? So one meal and I,
56:54you know.
56:55It's all haywire,
56:56so I you see what I'm saying.
56:58I think it really for the obesity thing.
57:00I mean,
57:00I do think that the NCIS responsibility
57:02to do research to understand and come
57:05up with strategies to mitigate it,
57:07recognizing that there are we may
57:08not get these other problems solved,
57:10but I think this is going to be a
57:12policy ultimately just like smoking.
57:16Thank you up and down.
57:19Actually, yeah, now I feel guilty about.
57:21I'm about to walk out and buy
57:221000 calories lunch right now.
57:24Thank you, but no thank you for so much for
57:26joining us and for your thoughts, were I.
57:29I hope it was provocative.
57:31I hope people got out a lot of it wasn't
57:33your typical scientific presentation,
57:35but I really wanted to get out and
57:37sort of encourage people to come to
57:39the division of cancer prevention
57:41with their new prevention ideas.
57:43We really need everybody in the boat.
57:46You know, coming up with new
57:49strategies to prevent cancer.
57:50I think the public deserves it.
57:54Absolutely well.
57:54Thank you so much all right.
57:56Good luck everyone.