Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally. Current treatments are morbid, even for patients who are cured, and there are over 13,000 deaths in the US from HNSCC annually. HPV-negative HNSCC is commonly resistant to DNA damaging therapy, EGFR inhibition and immunotherapy. HPV-associated tumors are highly treatment-responsive, but 20-30 percent recur. Even with immune checkpoint inhibition, the majority of these patients succumb.
The Yale Head and Neck SPORE (YHNSPORE) represents highly translational researchers with deep disease-based expertise who leverage the extraordinary scientific strength at Yale Cancer Center, to improve treatment for patients with this terrible malignancy. YHN-SPORE investigators have significantly impacted the field of HNSCC through training, and translational and clinical research. Basic scientists bring rigorous methodology to bear.
The YHN-SPORE seeks to address critical barriers to cure of HNSCC due to resistance to immune, DNA damaging and targeted therapy through these specific aims:
- Aim 1: To overcome resistance to EGFR inhibition in HNSCC by targeting active conformations of ErbB family members;
- Aim 2: To advance rational synthetic lethal combination therapy to the clinic in HPV-negative HNSCC;
- Aim 3: To advance combination demethylating therapy with immune checkpoint inhibition to the clinic for HPV-mediated HNSCC, with mechanistic studies and characterization of immune response;
- Aim 4: To bolster the foundation for HNSCC research through our Administrative, Biospecimen and Biostatistics/Bioinformatics cores, to engage institutional resources and the wider SPORE community; and
- Aim 5: To advance new research and to foster the next generation of HNSCC translational researchers through a Developmental Research Program, a Career Enhancement Program, and interaction and collaboration with the wider SPORE and HNSCC research communities.
The overarching theme of the 3 coordinated projects is overcoming treatment resistance, spanning mechanistic insights into resistance to current treatment modalities and immunotherapy; translational validation; human endpoints to underpin future trials of novel strategies to circumvent resistance; mechanistic confirmation in correlative studies; and clinical trials in HPV-negative and HPV-driven HNSCC.
Anticipated translational outcomes of the YHN-SPORE are:
- conformationally sensitive inhibitors to overcome resistance to EGFR inhibition in HNSCC;
- clinical safety and pharmacodynamic data combined aurora A kinase/WEE1 inhibition in HPV-negative HNSCC;
- proof-of concept and immunoprofiling data to support development of combined demethylation and immunotherapy in HPV-mediated HNSCC;
- novel models and genomically-characterized tumors to enable HNSCC translational research; and
- a diverse group of young investigators who will emerge as the generation who cure HNSCC.
The Yale Head and Neck SPORE draws on expertise from a distinguished group of internal and external advisors.
Internal Advisory Board:
Peter Glazer, MD (Chair of IAB), Chair of Therapeutic Radiology, Yale School of Medicine
George Bradt, Patient Advocate
Blossom Damania, PhD, Boshamer Distinguished Professor, Vice Dean for Research, UNC School of Medicine
Daniel DiMaio, MD, PhD, Waldemar Von Zedtwitz Professor of Genetics, Professor of Molecular Biophysics & Biochemistry and of Therapeutic Radiology
Ruth Halaban, PhD, Senior Research Scientist in Dermatology
Roy S. Herbst, MD, PhD, Ensign Professor of Medicine and Professor of Pharmacology; Chief of Medical Oncology; AD Translational Research, YCC; PI, Yale SPORE in Lung Cancer; (ex officio member)
Peter Krause, PhD, Patient Advocate. Senior Research Scientist in Epidemiology, in Medicine and in Pediatrics, and Lecturer in Epidemiology, Yale School of Public Health. Patient Advocate member, NCI HNSC
John A Ridge, MD, PhD. Professor and Vice-Chair of Surgery, FCCC; past President of the American Head and Neck Society; past Co-Chair of the NCI HNSC; Co-Chair, Surgical Oncology Committee NRG Oncology; Member, Previously Untreated Locally Advanced Task Force, NCI HNSC
External Advisory Board:
Jennifer Grandis, MD, (Chair of EAB) Vice-Chancellor, University of California San Francisco School of Medicine; Co-PI of the University of Pittsburgh HNC SPORE; and past Chair of the Inter-SPORE
Ezra E. W. Cohen, MD, Professor and AD, UCSD Moores Cancer Center. Leader of the UCSD Head and Neck SPORE application, and past Co-Chair of the NCI HNSC.
Paul Harari, MD, Professor and Chairman, Department of Human Oncology, University of Wisconsin. Principal Investigator for the Wisconsin Head and Neck SPORE.
Jeffrey Myers, MD, PhD, Professor of Surgery, MD Anderson Cancer Center. Leader, MD Anderson Head and Neck Program.
Sara Pai, MD, PhD, Associate Professor, Surgery, Harvard Medical School.
Yu Shyr, PhD, AD for Quantitative Sciences Integration, Vanderbilt Ingram Cancer Center; Harold L. Moses Professor of Cancer Research; Chair, Department of Biostatistics; Professor of Biostatistics, Biomedical Informatics & Health Policy; Director, Vanderbilt Center for Quantitative Sciences; Scientific Director, Quantitative SR.
John B. Sunwoo, MD, Professor Otolaryngology – Head & Neck Surgery Divisions, Stanford School of Medicine