Wafik S. El-Deiry, MD, PhD, FACP
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Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111
Deputy Cancer Center Director, Translational Research Program
Co-Leader, Molecular Therapeutics Program
Professor, Department Hematology/Oncology
William Wikoff Smith Endowed Chair in Cancer Research
American Cancer Society Research Professor
Colorectal cancer treatment; GI cancer; cancer genetics; drug resistance; tumor molecular profiling; Familial Polyposis; Hereditary Non-Polyposis Colon Cancer; Li-Fraumeni Syndrome; palliative care; circulating tumor cells; PK-guided dosing of chemotherapy
American Cancer Society Professorship
AACR Littlefield Award in metastatic colorectal cancer research, 2007
Howard Hughes Medical Institute Investigatorship, 1995-2004
I became a physician to help patients first-and-foremost, and I strive to excel in both the art and science of medicine. I listen to what my patients are saying and try to involve them in the decision-making because cancer therapy is now very personalized and so we must meet our patient’s goals. The doctor-patient relationship is very special and I try to serve as a strong advocate for my patients. I find that bringing the latest knowledge to patient care and seeing patients benefit is greatly rewarding.
As a physician-scientist I also conduct basic and clinical research to try and improve how we care for patients with cancer. It is very rewarding to think about clinical problems from the point of view of laboratory science, and to develop new ideas and translate them into new ways of diagnosing or treating cancer. I work to see a better day where what we offer patients is effective and less toxic therapy than what we have today. My goal is to discover and develop new drugs for patients with cancer. My group is also trying to improve how we monitor response to therapy in order to suggest new treatments if the present therapy is not working.
Dr. El-Deiry came to Fox Chase Cancer Center from the Penn State University, where he was the Rose Dunlap Professor of Medicine and Chief of the Hematology/Oncology Division, respectively, and the Associate Director for Translational Research and Program Leader of Experimental Therapeutics at the Penn State Hershey Cancer Institute. He served as Interim Cancer Center Director at Penn State in 2013-2014.
Prior to this, Dr. El-Deiry served on the faculty of the University of Pennsylvania School of Medicine, where he began as Assistant Professor of Medicine and Genetics in 1994 and rose to the rank of Professor of Medicine, Genetics, and Pharmacology with tenure by 2005. In addition, he served as Co-Program Leader of the Radiobiology & Imaging Program at Penn's Abramson Comprehensive Cancer Center between 2004 and 2010, and as Associate Director for Physician-Scientist Training in Hematology-Oncology at the University of Pennsylvania from 2007-2010. He was an investigator with the Howard Hughes Medical Institute at Penn from 1995-2004.
After earning his MD and a PhD in biochemistry at the University of Miami School of Medicine, Dr. El-Deiry completed an internal medicine residency at the Johns Hopkins Hospital and an oncology fellowship at the Johns Hopkins Oncology Center in Baltimore, Md. While there, he discovered p21 (WAF1) as a p53 target gene, universal cell cycle inhibitor, and tumor suppressor gene that for the first time explained the mammalian cell stress response—perhaps the most highly cited original work published in the journal Cell over the last 20 years.
Throughout his career, Dr. El-Deiry has continued research on the tumor suppressor pathways p53 and TRAIL—two important genes that regulate cell survival. This work led him to establish Oncoceutics, Inc. in 2004 and p53-Therapeutics, Inc. in 2013, companies devoted to the development of clinical therapeutics. ONC201/TIC10 a compound that emerged from small molecule screening in his laboratory, and for which he holds the original patent that was licensed to Oncoceutics, is in clinical trials as a first-in-class cancer therapeutic agent at multiple cancer centers including Fox Chase.
Dr. El-Deiry has co-authored more than 300 peer-reviewed publications and has served on many editorial boards, including those of the Journal of Clinical Investigation as well as Cancer Biology and Therapy, a publication he co-founded as Editor-in-Chief in 2001. He is an active participant in the National Institutes of Health peer-review system and is a Member of the American Cancer Society's Council for Extramural Grants. He serves as co-Chair of the Caris national Centers of Excellence Network in Precision Medicine and Chair of the Phase 1 Committee for development of early phase clinical protocols involving genomic analysis.
Dr. El-Deiry is a member of several national physician honor societies, including the Interurban Clinical Club started by Sir William Osler in 1905 (President, 2013-2014), American Society of Clinical Investigation, and American Association of Physicians. A fellow of the American College of Physicians, Dr. El-Deiry has organized several international meetings, including the International p53 Workshop and the International Conference on Tumor Progression and Therapeutic Resistance. He has won several awards, including the Michael S. Brown Junior Faculty Research Achievement Award from the University of Pennsylvania, the Elizabeth and John Cox Award for Molecular Advances in GI Diseases and Cancer from Georgetown University, the international Kuwait Prize in Applied Sciences for "Cancer Diseases," and the Dean's Award for Excellence in Teaching and the Department of Medicine's Excellence in Mentoring Award at the Penn State College of Medicine.
In 2014, Dr. El-Deiry was inducted into the Johns Hopkins University Society of Scholars.
- Fellow, Medical Oncology, Johns Hopkins Oncology Center, Baltimore, MD, 1994
- Resident, Internal Medicine, Johns Hopkins Hospital, Baltimore, MD, 1990
- MD/PhD, Biochemistry, University of Miami School of Medicine, Miami, FL, 1987
- BS, Chemistry, University of Miami, Coral Gables, FL, 1981
- Association of American Physicians, 2005
- President, Interurban Clinical Club 2013-2014
- American Society for Clinical Investigation, 1999
- American Association for Cancer Research, 1995
- American Society of Clinical Oncology, 1997
- Fellow, American College of Physicians, 2012
Honors & Awards
- Editor-in-Chief, Cancer Biology & Therapy
- Elected Member, The Johns Hopkins University Society of Scholars, 2014
- President, Interurban Clinical Club, 2013-2014
- Excellence in Mentoring Award, Department of Medicine, Penn State University, 2013
- Dean’s Award for Excellence in Teaching, Penn State College of Medicine, 2012
- Kuwait Prize in Applied Sciences for work on “Cancer Diseases,” 2010
- American Cancer Society Research Professorship, 2009-2018
- Cited in “America’s Top Oncologists” by the Consumer’s Research Council of America, 2008, 2009
- George and Mary J. Hamman Lectureship, MD Anderson Cancer Center, 2006
- Elected Member, Association of American Physicians, 2008
- ISI, Highly Cited Researcher in Molecular Biology and Genetics over 20 year period, 2005
- Elizabeth and John Cox Award for Molecular Advances in GI Diseases and Cancer, Georgetown University Medical Center, 2005
- Pioneer in Technology Award, Sbarro Health Research Organization, 2004
Maintaining an active lifestyle was always a priority for Todd Jackman, a professor of biology at Villanova University. He enjoyed running and was training for a half-marathon with his son. In the spring of 2014, he started experiencing bleeding which he attributed to hemorrhoids. Six months had passed with this ongoing symptom, and his wife urged him to go to the doctor.“I went to see my family doctor, who performed a physical,” recalls Todd.
- Gastrointestinal cancers, Drug Development, Precision Medicine
- Drug Development Targeting Cell Death in Colorectal & Other Cancers
Cell death signaling involving TRAIL death receptors and the p53 tumor suppressor gene/drug resistance mechanisms.
Novel therapeutics targeting mutant p53 in human cancer.
Combinatorial therapeutics and resistance mechanisms to ONC201/TIC10.
Liquid biopsy applications in cancer management.
Immunophenotyping Circulating tumor cells.
Precision Medicine; impact on genomics on cancer therapy.
Targeting the hypoxic tumor microenvironment.
Targeting cancer stem cells.
The El-Deiry Lab is a translational drug discovery and development lab focused on unraveling cell death signaling downstream of tumor suppressors p53 and TRAIL and development of novel cancer therapeutic approaches. The lab performs screening to discover new drugs, molecular and cellular analysis of drug mechanisms, live tumor growth and drug effectiveness studies, and clinical trial development for testing of new treatments for patients. The El-Deiry Lab’s approach for drug discovery and development is multi-tiered and involves understanding mechanisms of resistance through effects of the tumor microenvironment, hypoxia, cancer stem cells, repurposing available old drugs, finding new combinations for use of recently approved drugs, and conducting discovery work to find and develop new treatments. His expertise in the mechanisms of tumor suppressor genes has opened up new ways of finding cancer treatments.
p53 and TRAIL pathway mediated cell death & drug resistance. Dr. El-Deiry has focused on the how tumor cells die when treated with chemotherapy and how they become resistant to therapy. He discovered the consensus DNA binding site for p53 in the human genome (El-Deiry et al., Nature Genetics, 1992) and this paved the way for the identification of multiple effectors of p53 in tumor suppression. Among the most well-known p53 targets, El-Deiry discovered the universal cell cycle inhibitor p21(WAF1) (El-Deiry et al., Cell, 1993) and the TRAIL death receptor DR5 (Wu et al., Nature Genetics, 1997) as important mediators of tumor suppression following exposure of cells to radiation or chemotherapy. His lab created a knock-out mouse for TRAIL receptor DR5 (Finnberg et al., Mol. Cell. Biol., 2005; Finnberg et al., J. Clin. Invest., 2008) and this mouse is tumor prone and develops an inflammatory syndrome in the lungs and gut after sub-lethal irradiation. El-Deiry identified c-Myc as a major determinant of TRAIL sensitivity (Ricci et al., Mol. Cell. Biol., 2004) and was the first to demonstrate synergy between TRAIL therapy and the multi-kinase inhibitor sorafenib (Ricci et al., Cancer Cell, 2007).
ONC201/TIC10. The El-Deiry Lab discovered ONC201/TIC10 as a first-in-class TRAIL pathway inducer that is orally bioavailable and crosses the blood-brain barrier to treat brain tumors (Allen et al., Science Translational Medicine, 2013). TRAIL and Foxo3a are required for the anti-tumor effect of TIC10. The compound has anti-tumor effects as a single agent in multiple animal models including immunocompetent lymphoma models and subcutaneous models of colorectal, breast, lung cancer, or glioblastoma. ONC201/TIC10 has synergy with other agents as well as effects against cancer stem cells (Prabhu et al., Cancer Research, 2015) that often lead to relapse and resistance to chemotherapy. ONC201/TIC10 has completed a human phase I trial and has moved into additional phase I/II clinical trials at multiple centers including at Fox Chase.
p53 pathway restoration. Dr. El-Deiry’s lab has performed drug screening to restore p53 signaling in mutant p53-expressing tumors. This project started in 2002 in his lab and has made progress to find promising drug candidates. Among the most interesting leads are small molecules that can stimulate p73 (Wang et al., Proc. Natl. Acad. Sci., 2006; Hong et al., Cancer Research, 2014), disrupt mutant p53:p73 interaction (Hong et al., Cancer Research, 2014), and target mutant p53 for degradation (Zhang et al., Cancer Research, 2015). Research on therapeutic restoration of the p53 pathway represents a major continuing direction in Dr. El-Deiry’s laboratory.
Targeting the hypoxic tumor microenvironment. One of the major obstacles in cancer therapy is resistance mediated by tumor hypoxia. Dr. El-Deiry’s lab performed a chemical screen for drug candidates that can act as hypoxia sensitizers and synergize with TRAIL or 5-Fluorouracil to kill colorectal tumors (Mayes et al., Cancer Research, 2011). His group identified sangivamycin-like molecules (SLMs), nucleoside analogues as novel hypoxia sensitizers in vivo with impressive anti-tumor effects. This approach holds promise to improve the way current therapy is being used and he is continuing to translate these discoveries to the clinic and to develop biomarkers studies to facilitate the translation. His lab demonstrated a novel regulation of HIF stability through CDK activity, a previously unknown regulatory mechanism that has important therapeutic implications (Warfel et al., Cell Cycle, 2013).
Other areas of interest in the El-Deiry Lab include targeting cancer stem cells, CTC immuno-phenotyping, liquid biopsy approaches, translational projects involving tumor genomic profiling and precision medicine. Please make an appointment to discuss if interested.
David Dicker (Lab Manager, Technical Director for flow, imaging and CTC analysis)
Alison Conn (Executive Assistant)
Niklas Finnberg, PhD (Assistant Professor)
Shengliang Zhang, MD, PhD (Assistant Professor)
Lanlan Zhou, MD, PhD (post-doctoral fellow)
Elizabeth Matthew, PhD (Assistant Professor)
Varun V. Prabhu (graduate student; Penn State University)
Leah Kline, PhD (post-doctoral fellow)
Prashanth Gokare (graduate student; Penn State University)
Liz Hernandez (masters student; Penn State University)
Amriti Lulla (graduate student; Penn State University)
Shuai Zhao (graduate student; Temple University)
Jessica Wagner (graduate student; Temple University)
Xiaobing Tian, PhD (post-doctoral scientist)
Marie Baumeister (MD/PhD student; Temple University)
Junaid Abdulghani, MD, PhD (Assistant Professor)
Avital Lev, PhD (staff scientist)
Safoora Deihimi (masters student; Drexel University)
Zhang, S., Zhou, L., Hong, B., van den Heuvel, A.P.J., Prabhu, V.V., Warfel, N.A., Kline, C.L.B., Dicker, D.T., Kopelovich, L., and El-Deiry, W.S. Small-molecule NSC59984 restores p53 pathway signaling and antitumor effects against colorectal cancer via p73 activation and degradation of mutant p53. Cancer Res., 75:3842-3852, 2015. PubMed
Li, P., Mao., Z., Peng, Z., Zhou, L., Chen, Y., Huang, P-H., Truica, C.I., Drabick, J.J., El-Deiry, W.S., Dao, M., Suresh, S., and Huang T.J. Acoustic separation of circulating tumor cells. Proc. Natl. Acad. Sci. USA, 112:4970-4975, 2015. PubMed
Prabhu, V.V., Allen, J.E., Dicker, D.T., El-Deiry, W.S. Small molecule ONC201/TIC10 targets chemotherapy-resistant colorectal cancer stem-like cells in an Akt/Foxo3a/TRAIL-dependent manner. Cancer Res., 75:1423-1432, 2015. PubMed
Allen, J.E., Prabhu, V.V., Talekar, M., van den Huevel, P., Lim, B., Dicker, D.T., Fritz, J.L., Beck, A., and El-Deiry, W.S. Genetic and pharmacological screens converge in identifying FLIP, Bcl-2 and IAP proteins as key regulators of sensitivity to the TRAIL-inducing anti-cancer agent ONC201/TIC10. Cancer Research, 75:1668-1674, 2015. PubMed
Wagner, J., Kline, C.L., Pottorf, R.S., Nallaganchu, B.R., Olson, G.L., Dicker, D.T., Allen, J.E., and El-Deiry, W.S. The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity. Oncotarget, 5:12728-12737, 2014. PubMed
Hong, B., Prabhu, V.V., Zhang, S., van den Heuvel, A.P.J., Dicker, D.T., Kopelovich, L., and El-Deiry, W.S. Prodigiosin rescues deficient p53 signaling and anti-tumor effects via up-regulating p73 and disrupting its interaction with mutant p53. Cancer Research, 74:1153-1165, 2014. PubMed
Kline, C.L., Schiccitano, A., Zhu, J., Beachler, C., Sheikh, H., Harvey, H., Mackley, H., McKenna, K., Staveley-O’Carroll, K., Poritz, L., Mesaris, E., Stewart, D., Sivik, J., and El-Deiry, W.S. Personalized dosing via pharmacokinetic monitoring of 5-Fluorouracil might reduce toxicity in early- or late-stage colorectal cancer patients treated with infusional 5-Fluorouracil-based chemotherapy regimens. Clinical Colorectal Cancer, 13:119-126, 2014. PubMed
Warfel, N.A., Dolloff, N.G., Dicker, D.T., Malysz, J., and El-Deiry, W.S. CDK1 stabilizes HIF-1a via direct phosphorylation of Ser668 to promote tumor growth. Cell Cycle, 12:3689-3701, 2013. PubMed
Gallant, J-N., Matthew, E.M., Cheng, H., Harouaka, R., Lamparella, N.E., Kunkel, M., Yang, Z., Harvey, H.A., Cream, L.V., Kumar, S.M., Robertson, G.P., Zheng, S., Drabick, J.J., Truica, C.I., and El-Deiry, W.S. Predicting therapy response in live tumor cells isolated with the flexible micro spring array device. Cell Cycle, 12:2132-2143, 2013. PubMed
Allen, J.E., Krigsfeld, G., Mayes, P.A., Patel, L., Dicker, D.T., Patel, A.S., Dolloff, N.G., Messaris, E., Scata, K.A., Wang, W., Zhou, J-Y., Wu, G.S. and El-Deiry, W.S. Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction and potent anti-tumor effects. Science Translational Medicine, 5:50-62, 2013. PubMed