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Wafik S. El-Deiry, MD, PhD, FACP

Wafik S. El-Deiry, MD, PhD, FACP

Clinical Locations

Primary Location

Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111

About

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

 

Specialties

Treatment Focus

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

Research Program

Key Awards

American Cancer Society Professorship      

AACR Littlefield Award in metastatic colorectal cancer research, 2007  

Howard Hughes Medical Institute Investigatorship, 1995-2004      

Treatment Philosophy

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.

Follow on Twitter: @weldeiry

Deputy Cancer Center Director for Translational Research

Dr. El-Deiry leads the Fox Chase translational research efforts and continues his work in the world of translational drug discovery and development. 

Dr. El-Deiry is a practicing physician-scientist who sees patients with colorectal cancer and whose research laboratory focuses on developing novel therapeutics targeting cell death pathways. He is one of only 40 active American Cancer Society Research Professors—a prestigious distinction providing funding to investigators having made seminal contributions to cancer research, and for efforts in mentoring, service and advocacy... Expand

Education, Training & Credentials

Educational Background

  • 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

Memberships

  • 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
Patient Stories

Todd Jackman

Colorectal Cancer

Todd Jackman

Colorectal Cancer

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.

Research Profile

Research Program

Research Interests

  • 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.

Lab Overview

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.

Additional Staff

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)

Publications

Selected Publications

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

Additional Publications

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