SCIENTICFIC ADVISORY BOARD
Laura Attardi
PhD
Stanford University
Professor of Radiation Oncology and Genetics
The overarching goal of Dr. Attardi’s research is to better define the mechanisms by which the p53 protein promotes different responses in different settings, ranging from tumor suppression to responses to chemotherapeutics, using the mouse as an in vivo model system, with the ultimate goal of gaining insight that may facilitate clinical advances in diagnosis, prognostication and therapy.
The observations that the p53 gene is mutated in at least half of all human cancers of a wide variety of types and that p53 null mice develop cancer at 100% frequency together underscore the critical role for p53 in tumor suppression. Wild-type p53 is a cellular stress sensor, responding to diverse insults such as DNA damage, hyperproliferative signals, and hypoxia by inducing growth arrest or apoptosis, responses thought to be important to tumor suppression. Dr. Attardi utilizes a combination of mouse genetic, cell biological, biochemical, and genomic approaches to address and understand how p53 acts mechanistically. She is deciphering the transcriptional networks responsible for mediating p53 functions in different contexts, an understanding that will help us understand how to best promote the beneficial and minimize the detrimental effects of p53 in the clinic.
Her work includes defining the transcriptional networks responsible for tumor suppression, using CRISPR/Cas9 and shRNA high-throughput genetic screening approaches, identifying p53-interacting partners by mass spectrometry approaches, elucidating the genes activated and repressed by p53 in diverse settings using genomic technologies such as ChIP-sequencing and RNA-sequencing, to understand how p53 drives different responses among other projects.
Fred Bunz
MD, PhD
Johns Hopkins University
Associate Professor of Radiation Oncology and Molecular Radiation Sciences
Dr. Bunz’s research objective is to understand how stress-activated signaling pathways affect the cellular responses to anti-cancer therapy. A longstanding interest is p53, a central node within a complex network of DNA damage-response pathways involved in tumor suppression. It is well-known that cancer associated p53 mutations impact the efficacy of DNA damage-based anticancer therapies, such as radiotherapy.
It is now apparent that p53 also controls immune recognition, and thereby influences the efficacy of immune-based therapies. Recent work in the lab is focused on understanding the mechanistic basis for these effects, and on the development of therapeutic viral agents that can stimulate neoantigen-specific anti-cancer immune responses.
The long-term goal is to better understand how current therapies work, and to develop new and improved cancer treatments.
Timothy F. Burns
MD, PhD
University of Pittsburgh Hillman Cancer Center
Associate Professor of Medicine
Dr. Burns’ research and clinical interests revolve around the development of targeted therapies for KRAS-mutant NSCLC as well as novel strategies to overcome resistance to targeted therapies for EGFR-mutant and MET-altered NSCLC. My three main research themes are 1) novel pre-clinical target validation and drug development (TWIST1 in oncogene driven NSCLC and TKI resistance; targeting metabolism in oncogene driven lung cancer); and 2) elucidating mechanisms of resistance for targeted inhibitors to develop rationale therapeutic combinations that can be tested in the clinic and 3) development of targeted therapy approaches for the treatment of brain metastases.
He is interested in mechanisms of resistance to targeted agents currently in phase 1 and 2 trials to develop rational therapeutic combinations in the clinic. He has a focus on brain metastases and is exploring targeting the HGF-MET-TWIST1 pathway or downstream metabolic pathways that may be effective strategies for preventing or treating lung brain metastases. In addition to preclinical studies, he is using radiogenomic and cell free DNA approaches to predict molecular phenotypes of brain metastases to identify patients with brain metastases that can benefit from targeted therapy in the clinic.
Dr. Burns completed his PhD studies in the MD/PhD Program at University of Pennsylvania by 2005 where he focused on the tumor suppressive function of p53 including underlying mechanisms and therapeutic opportunities.
Keith Flaherty
MD
Harvard University
Professor, Medicine, Harvard Medical School, Director of Henri and Belinda Termeer Center for Targeted Therapy, Director of Clinical Research, Cancer Center, Massachusetts General Hospital
Dr. Flaherty’s research focuses on the understanding of novel, molecularly targeted therapies in cancer. In this context he focused on the development of response and predictive biomarkers to define the mechanisms of action and resistance of novel therapies, as well as to identify the optimal target population.
Elsa Flores
PhD
Moffitt Cancer Center
Associate Center Director, Basic Science
Dr. Flores’ laboratory is working to understand the p53 family pathway in order to target this pathway therapeutically when it is mutated in cancer. As a basic scientist, her lab has made important discoveries in understanding the functions of the p53 family and its family members. Dr. Flores is unraveling the overlapping and unique activities of the p53 family in human cancer using mouse models and patient derived tumors. p53 is commonly mutated in human cancer and has been difficult to target therapeutically in cancer.
This is due to the complex network of genes regulated by p53 and the extensive interactions with its family members, p63 and p73. Prior to her work, very little was known about p63 and p73 function in cancer. She has demonstrated that p63 and p73 are required for p53 to induce apoptosis in response to DNA damage, which is critical for the response to chemo- and radiation therapy of tumors. Additionally, her laboratory generated genetically engineered mouse models mutant for isoforms of p63 and p73 and provided the first evidence that p63 and p73 are potent suppressors of tumorigenesis and metastasis.
Using her mouse models her group unveiled previously unappreciated functions for TAp63, which she identified as the tumor suppressive isoform of p63 in mouse and human tumors, and ∆Np63, the oncogenic isoform, in the regulation of microRNA biogenesis, stem cell maintenance, aging, and metabolism. She has also found that TAp63 and TAp73 can compensate for p53 function in vivo and found that inhibition of ∆Np63 or ∆Np73 leads to tumor regression in p53-/- mice by upregulation of TAp63 and TAp73 function and metabolic reprogramming within those tumors. The work from her laboratory indicates that the inter-related functions of the p53 family members must be understood for effective therapy of tumors with alterations in the p53 pathway.
Her group is poised to make further advances in understanding the molecular mechanisms employed by this gene family in multiple biological processes and is currently using genomic approaches to understand the regulation of multiple downstream pathways of the p53 family including the functions and regulation of long non-coding RNAs in multiple cancers, stem cell regulation, and tumor metabolism.
Roy S. Herbst
MD, PhD
Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology. Deputy Director, Yale Cancer CenterChief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital. Assistant Dean for Translational Research, Yale School of Medicine. Director, Center for Thoracic Cancers, Yale Cancer Center and Smilow Cancer Hospital. Program Director, Master of Health Science – Clinical Investigation Track (MHS-CI).
Dr. Herbst is nationally recognized for his leadership and expertise in lung cancer treatment and research. He is best known for his work in developmental therapeutics and the personalized therapy of non-small cell lung cancer, in particular the process of linking genetic abnormalities of cancer cells to novel therapies.
Dr. Herbst says the way to a cure is understanding how cancer grows and finding new targets and new immunologic ways to enhance therapy to treat it. He adds that understanding and preventing metastasis and treatment resistance—two factors that often result in cancer fatality—is critical to our ability to increase survivorship rates. e has worked over several decades as a pioneer of personalized medicine and immunotherapy to identify biomarkers and bring novel targeted treatments and immunotherapies to patients, serving as principal investigator for numerous clinical trials testing these agents in advanced stage lung cancers.
This work led to the approval of several therapies (such as gefitinib, cetuximab, bevacizumab, axitinib), which have revolutionized the field and greatly enhanced patient survival. He and his Yale colleagues were among the first to describe the PD-1/PD-L1 adaptive immune response in early phase trials and to offer trials of PD-L1 inhibitors atezolizumab and pembrolizumab to lung cancer patients. His leadership in targeted therapeutics resulted in being selected for ASCO’s plenary presentation in 2020 and 2023 and publication of results of the third-generation EGFR-inhibitor osimertinib for the treatment of resected EGFR-mutant NSCLC in the New England Journal of Medicine.
Razelle Kurzrock
MD
Medical College of Wisconsin
Linda T. and John A. Mellowes Endowed Chair of Precision Oncology, Professor of Medicine and Associate Director of Clinical Research, MCW Cancer Center and Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine
Dr. Kurzrock is a world-renowned leader in precision oncology and rare cancers research. She is the Associate Director of Clinical Research for the Medical College of Wisconsin Cancer Center, Associate Director of Precision Oncology at the Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine and the founding director of the Michels Rare Cancers Research Laboratories at the MCW Cancer Center. She is recognized as one of the world’s 25 most important voices in precision medicine and one of the most highly cited scientists globally.
She has authored over 950 scientific and medical publications. Dr. Kurzrock is the Chair for the Early Therapeutics and Rare Cancers Committee (SWOG NCI) — one of the largest clinical trials cooperative groups in the country — and has been the principal investigator for more than 100 early-phase clinical trials, leading eight life-changing drugs to FDA approval. In 2022, Dr. Kurzrock and the DART rare cancer study team received the National Cancer Institute Director’s Award of Merit for outstanding work.
Vivek Subbiah
MD
Sarah Cannon Research Institute
Chief, Early-Phase Drug Development
Dr. Subbiah joined Sarah Cannon Research Institute (SCRI) in 2023. In his role, Dr. Subbiah oversees SCRI’s nine drug development units and leads the expansion of early-phase capabilities and programs across SCRI’s growing research network of more than 1,300 physicians at more than 250 locations in 24 states. Previously, Dr. Vivek Subbiah was at the University of Texas MD Anderson Cancer Center where he was an associate professor in the Department of Investigational Cancer Therapeutics.
During his near 15-year tenure there, Dr. Vivek Subbiah held several leadership roles including executive director, Medical Oncology Research, MD Anderson Cancer Network as well as clinical medical director, Division of Cancer Medicine where he oversaw both the outpatient and inpatient clinical care delivery operations for the Phase I program. Dr. Subbiah has served as the principal investigator in over 100 phase I/II trials and co-investigator in over 200 clinical trials and is known for his leadership in several first-in-human and practice-changing studies that directly led to approvals from the FDA, European Medicines Agency, and other agencies across the world.
He is an expert in tumor agnostic precision oncology and lead the BRAF and RET tissue agnostic studies to FDA approval. He has authored over 400 peer-reviewed publications in several high-impact journals such as The New England Journal of Medicine, Nature Medicine, Journal of Clinical Oncology, JAMA Oncology, Cancer Discovery, Lancet Oncology, Nature Reviews Clinical Oncology, Lancet Diabetes and Endocrinology, and Clinical Cancer Research.