Wafik El-Deiry

Wafik El-Deiry (born, 1961) is an American physician and cancer researcher who is the Associate Dean for Oncologic Sciences at the Warren Alpert Medical School, Brown University and the Director of the Joint Program in Cancer Biology at Brown University and its affiliated hospitals.[1] He was previously Deputy Director of Translational Research at Fox Chase Cancer Center, where he was also co-Leader of the Molecular Therapeutics Program.[2]

Wafik El-Deiry
Education
    Scientific career
    Institutions

    Career

    El-Deiry was formerly a Professor of Medicine and Chief of Hematology/Oncology at the Penn State Milton S. Hershey Medical Center. He also served as the Associate Director for Translational Research and Interim Cancer Center Director at Penn State University.[3] Prior to his tenure at Penn State, he was an investigator in cell biology at the Howard Hughes Medical Institute and a professor of medicine, genetics, and pharmacology at the University of Pennsylvania School of Medicine. While at the University of Pennsylvania, Dr. El-Deiry served as co-Leader of the Radiobiology & Imaging Program at the Abramson Cancer Center and as Associate Director for Physician-Scientist training in Hematology/Oncology.[4] He held an endowed chair in hematology-oncology while at Penn State University: the Rose Dunlap Division Chair in Hematology-Oncology.[5] At Fox Chase Cancer Center, he holds the William Wikoff Smith Chair in Cancer Research.[6][7] El-Deiry earned MD and PhD degrees from the University of Miami Miller School of Medicine in 1987 and later delivered the Keynote presentation at the 9th Annual MD/PhD Student Research Symposium.[8][9]

    Research

    El-Deiry is among the top 40 most-cited researchers of the 1990s,[10] having authored 13 papers that have been cited over 6,000 times. His paper, "WAF1, a potential mediator of p53 tumor suppression",[11] which has been cited over 9,000 times according to Google Scholar,[12] is among the top 10 most-cited papers of the 1990s. El-Deiry discovered the genomic DNA binding site for the tumor suppressor p53.[13] Nikola Pavletich later crystallized the DNA-binding domain of p53 with the DNA binding site and showed that p53 amino acid residues involved in mutations in human cancer normally touch the DNA binding site recognized by the p53 protein.[14] El-Deiry made the discoveries of the consensus binding site for p53 and the discovery of WAF1 while working with Bert Vogelstein at Johns Hopkins University. p21(WAF1) was the first mammalian cell cycle inhibitor to be discovered, and was found independently by Wade Harper and Steve Elledge as a CDK2-interacting protein p21(CIP1),[15] Yue Xiong and David Beach as a cyclin-CDK-PCNA interacting protein (p21),[16] and as a senescence derived inhibitor by Noda.[17] Multiple CDK inhibitors have become approved as cancer therapeutics, including palbociclib, abemaciclib and ribociclib. In 2017, El-Deiry's group discovered a micro-RNA family that inhibits CDK4/6.[18][19]

    In total, El-Deiry has >61,000 citations and an H-index of 114 according to Google Scholar.[12] He was recognized through an award from the American Cancer Society in 2016.[20]

    As an independent investigator at University of Pennsylvania, El-Deiry discovered TRAIL death receptor 5 (DR5)[21][22] in 1997. His group was first to combine gene silencing with bioluminescence imaging in vivo[23][24] and to use molecular imaging for drug screening.[25] His group created a knockout mouse of death receptor 5 (DR5) that shows reduced apoptosis in vivo after exposure to gamma-radiation,[26] and increased tumor susceptibility in tumor-prone genetic backgrounds.[27] The mechanism by which cell death occurs in vivo after radiation or other DNA damage has remained an important question that has been studied by Michael B. Kastan, Scott W. Lowe, Karen Vousden, and others. El-Deiry's contribution was to define the role of the extrinsic cell death pathway through p53 regulation of death receptor 5.

    El-Deiry worked on drug synergies and discovered a potent cancer therapeutic interaction between TRAIL and sorafenib.[28][29] In 2013, his group reported a TRAIL-inducing compound TIC10 as a novel cancer therapeutic and dual inhibitor of ERK and Akt.[30] TIC10 (also known as ONC201) could cross the blood-brain barrier and treat glioblastoma brain cancer in mice.[31] Glioblastoma is a difficult to treat cancer with a high mortality rate. ONC201 is being tested in the clinic at Massachusetts General Hospital and New York University with some evidence of response in patients with glioblastoma.[32][33] By 2016, TIC10 was found to trigger an integrated stress response leading to anti-tumor effects.[34] ONC201/TIC10 is active against cancer stem cells[35] and blocks cancer stem cell gene signatures.[36][37] ONC201 can bind a subtype of dopamine receptors.[38] Unlike TRAIL which is active against a subset of triple negative breast cancer (TNBC), ONC201 has preclinical anti-tumor efficacy against ER/PR+. Her2+ and TNBC.[39] Analogues of ONC201, including ONC206 and ONC212 have been described and demonstrate some differential activities as compared to ONC201.[40][41] ONC212 has preclinical activity in pancreatic cancer, liver cancer and melanoma.[40][41]

    Professional activities

    As an American Cancer Society Research Professor,[42] El-Deiry was introduced and spoke at a Relay for Life event in Pennsylvania in 2017.[43][44]

    In 2001, El-Deiry became the Founding Editor-in-Chief of the peer-reviewed journal Cancer Biology and Therapy.[45]

    El-Deiry is a member of the F1000 faculty.[46] He serves as a Member of the Editorial Board of the oncology newspaper HemOnc Today.[47]

    In 2005, El-Deiry became a member of the Interurban Clinical Club,[48] and served as its President in 2013–2014. He is also a member of the American Society for Clinical Investigation (1999), the Association of American Physicians (2008), is a Fellow of the American College of Physicians (2012), and a member of the Johns Hopkins University Society of Scholars (2014).[49][50]

    In June, 2015 El-Deiry described the developments in liquid biopsy for the American Association for Cancer Research's blog CancerResearch Catalyst.[51] In August, 2015 El-Deiry gave an interview to Yahoo Lifestyle about former President Carter's melanoma that had spread to his brain.[52] He also spoke with Health News Reporter Ali Gorman at Fox Chase in Philadelphia, Pennsylvania on 8-20-15 regarding President Jimmy Carter's Diagnosis of metastatic melanoma.[53]

    In February, 2016 he spoke with US News and World Report about targeted cancer therapy for genetic discoveries.[54] El-Deiry commented for the Washington Post in June, 2016 about the Cancer Moonshot spearheaded by then Vice President Joseph Biden,[55] and organized an event in Philadelphia.[56] El-Deiry advocated for broadening clinical trial enrollment criteria to be more inclusive.[57]

    As a medical oncologist El-Deiry specializes in the care of patients with colorectal cancer. His clinical research demonstrated variability in 5-fluorouracil plasma levels in patients with colorectal cancer.[58] El-Deiry showed that pharmacokinetically-guided dosing of 5-fluorouracil chemotherapy is associated with lower levels of toxicity among patients with stage II/III as well as stage IV colorectal cancer.[59][60] Toxicity from chemotherapy is associated with worse quality of life in patients with cancer. In 2017, his group showed that the tumor suppressor protein p53 represses the DPYD gene in 5-fluorouracil-treated cells and that tumor cells with mutated p53 have higher levels of DPYD thereby becoming resistant to 5-fluorouracil.[61] DPYD is involved in the metabolism of 5-fluorouracil and patients with DPD-deficiency have predictable toxicity from 5-fluorouracil. El-Deiry advises adopting a healthy diet including cutting back on pro-inflammatory foods to reduce the risk of colorectal cancer.[62] He discusses in detail and endorses findings that tree nut consumption reduces the risk of recurrence and promotes improved survival in patients with stage III colon cancer.[63] El-Deiry spoke about the benefits of tree nut consumption with a Philadelphia CBS local news station that shared the news.[64] He further argues for the use of CEA as an inexpensive and useful blood-based marker to follow when possible to monitor colorectal cancer disease burden and progress after surgery or chemotherapy.[65] He provides his perspective on the use of maintenance chemotherapy in colorectal cancer.[66]

    El-Deiry is the scientific Founder of Oncoceutics.[67]

    Personal life

    El-Deiry is a husband to wife Evelyn, and father to four kids James, John, Jennifer and Julie.

    References

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    12. "Wafik El-Deiry - Google Scholar Citations". scholar.google.com.
    13. El-Deiry, Wafik S.; Kern, Scott E.; Pietenpol, Jennifer A.; Kinzler, Kenneth W.; Vogelstein, Bert (1992). "Definition of a consensus binding site for p53". Nature Genetics. 1 (1): 45–49. doi:10.1038/ng0492-45. ISSN 1546-1718. PMID 1301998.
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    19. Lulla, Amriti R.; Slifker, Michael J.; Zhou, Yan; Lev, Avital; Einarson, Margret B.; Dicker, David T.; El-Deiry, Wafik S. (2017-12-15). "miR-6883 Family miRNAs Target CDK4/6 to Induce G1 Phase Cell-Cycle Arrest in Colon Cancer Cells". Cancer Research. 77 (24): 6902–6913. doi:10.1158/0008-5472.can-17-1767. PMID 29061672.
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    23. "Molecular Tailoring Of Chemotherapy With Novel Imaging Techniques".
    24. Wang, Shulin; El-Deiry, Wafik S. (2004-09-15). "Inducible Silencing of KILLER/DR5 In vivo Promotes Bioluminescent Colon Tumor Xenograft Growth and Confers Resistance to Chemotherapeutic Agent 5-Fluorouracil". Cancer Research. 64 (18): 6666–6672. doi:10.1158/0008-5472.can-04-1734. PMID 15374982.
    25. Wang, Wenge; Kim, Seok-Hyun; El-Deiry, Wafik S. (2006-07-18). "Small-molecule modulators of p53 family signaling and antitumor effects in p53-deficient human colon tumor xenografts". Proceedings of the National Academy of Sciences. 103 (29): 11003–11008. Bibcode:2006PNAS..10311003W. doi:10.1073/pnas.0604507103. ISSN 0027-8424. PMC 1544164. PMID 16835297.
    26. Finnberg, Niklas; Gruber, Joshua J.; Fei, Peiwen; Rudolph, Dorothea; Bric, Anka; Kim, Seok-Hyun; Burns, Timothy F.; Ajuha, Hope; Page, Robert (2005-03-01). "DR5 Knockout Mice Are Compromised in Radiation-Induced Apoptosis". Molecular and Cellular Biology. 25 (5): 2000–2013. doi:10.1128/mcb.25.5.2000-2013.2005. ISSN 0270-7306. PMC 549384. PMID 15713653.
    27. Finnberg, Niklas; Klein-Szanto, Andres J.P.; El-Deiry, Wafik S. (2008). "TRAIL-R deficiency in mice promotes susceptibility to chronic inflammation and tumorigenesis". Journal of Clinical Investigation. 118 (1): 111–123. doi:10.1172/jci29900. PMC 2129232. PMID 18079962.
    28. Ricci, M. Stacey; Kim, Seok-Hyun; Ogi, Kazuhiro; Plastaras, John P.; Ling, Jianhua; Wang, Wenge; Jin, Zhaoyu; Liu, Yingqiu Y.; Dicker, David T. (2007). "Reduction of TRAIL-Induced Mcl-1 and cIAP2 by c-Myc or Sorafenib Sensitizes Resistant Human Cancer Cells to TRAIL-Induced Death". Cancer Cell. 12 (1): 66–80. doi:10.1016/j.ccr.2007.05.006. PMID 17613437.
    29. Kim, Seok-Hyun; Ricci, M. Stacey; El-Deiry, Wafik S. (2008-04-01). "Mcl-1: A Gateway to TRAIL Sensitization". Cancer Research. 68 (7): 2062–2064. doi:10.1158/0008-5472.can-07-6278. PMID 18381408.
    30. Allen, Joshua E.; Krigsfeld, Gabriel; Mayes, Patrick A.; Patel, Luv; Dicker, David T.; Patel, Akshal S.; Dolloff, Nathan G.; Messaris, Evangelos; Scata, Kimberly A. (2013-02-06). "Dual Inactivation of Akt and ERK by TIC10 Signals Foxo3a Nuclear Translocation, TRAIL Gene Induction, and Potent Antitumor Effects". Science Translational Medicine. 5 (171): 171ra17. doi:10.1126/scitranslmed.3004828. ISSN 1946-6234. PMC 4535715. PMID 23390247.
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    32. Arrillaga-Romany, Isabel; Chi, Andrew S.; Allen, Joshua E.; Oster, Wolfgang; Wen, Patrick Y.; Batchelor, Tracy T. (2017-05-12). "A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma". Oncotarget. 8 (45): 79298–79304. doi:10.18632/oncotarget.17837. ISSN 1949-2553. PMC 5668041. PMID 29108308.
    33. Ralff, Marie D.; Lulla, Amriti R.; Wagner, Jessica; El-Deiry, Wafik S. (2017-10-13). "ONC201: a new treatment option being tested clinically for recurrent glioblastoma". Translational Cancer Research. 6 (S7): S1239–S1243. doi:10.21037/tcr.2017.10.03. ISSN 2219-6803. PMC 6117120. PMID 30175049.
    34. Kline, C. Leah B.; Van den Heuvel, A. Pieter J.; Allen, Joshua E.; Prabhu, Varun V.; Dicker, David T.; El-Deiry, Wafik S. (2016-02-16). "ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases". Science Signaling. 9 (415): ra18. doi:10.1126/scisignal.aac4374. PMC 4968406. PMID 26884600.
    35. Prabhu, Varun V.; Allen, Joshua E.; Dicker, David T.; El-Deiry, Wafik S. (2015-04-01). "Small-Molecule ONC201/TIC10 Targets Chemotherapy-Resistant Colorectal Cancer Stem–like Cells in an Akt/Foxo3a/TRAIL–Dependent Manner". Cancer Research. 75 (7): 1423–1432. doi:10.1158/0008-5472.can-13-3451. PMC 4537643. PMID 25712124.
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    39. Ralff, Marie D.; Kline, Christina L. B.; Küçükkase, Ozan C.; Wagner, Jessica; Lim, Bora; Dicker, David T.; Prabhu, Varun V.; Oster, Wolfgang; El-Deiry, Wafik S. (2017-07-01). "ONC201 Demonstrates Antitumor Effects in Both Triple-Negative and Non–Triple-Negative Breast Cancers through TRAIL-Dependent and TRAIL-Independent Mechanisms". Molecular Cancer Therapeutics. 16 (7): 1290–1298. doi:10.1158/1535-7163.mct-17-0121. PMC 5564301. PMID 28424227.
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    41. Lev, Avital; Lulla, Amriti R.; Wagner, Jessica; Ralff, Marie D.; Kiehl, Joshua B.; Zhou, Yan; Benes, Cyril H.; Prabhu, Varun V.; Oster, Wolfgang (2017-09-12). "Anti-pancreatic cancer activity of ONC212 involves the unfolded protein response (UPR) and is reduced by IGF1-R and GRP78/BIP". Oncotarget. 8 (47): 81776–81793. doi:10.18632/oncotarget.20819. ISSN 1949-2553. PMC 5669847. PMID 29137221.
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    52. "Melanoma Found in Jimmy Carter's Brain: How Can a Skin Cancer Develop Inside The Body?".
    53. "Dr. Wafik El-Deiry, MD, PhD, FACP, talks to Ali Gorman about President Jimmy Carter's cancer prognosis on 6ABC Action News at 5 p.m. on August 20, 2015".
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    58. Kline, Christina Leah; Sheikh, Hassan S.; Scicchitano, Angelique; Gingrich, Rebecca; Beachler, Cheryl; Finnberg, Niklas K.; Liao, Jason; Sivik, Jeffrey; El-Deiry, Wafik S. (2011-10-01). "Preliminary observations indicate variable patterns of plasma 5-fluorouracil (5-FU) levels during dose optimization of infusional 5-FU in colorectal cancer patients". Cancer Biology & Therapy. 12 (7): 557–568. doi:10.4161/cbt.12.7.18059. ISSN 1555-8576. PMID 21931273.
    59. Kline, Christina Leah B.; Schiccitano, Angelique; Zhu, Junjia; Beachler, Cheryl; Sheikh, Hassan; Harvey, Harold A.; Mackley, Heath B.; McKenna, Kevin; Staveley-O'Carroll, Kevin (2014). "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 (2): 119–126. doi:10.1016/j.clcc.2013.11.001. PMID 24461492.
    60. Kline, Christina Leah B.; El-Deiry, Wafik S. (2013-08-21). "Personalizing Colon Cancer Therapeutics: Targeting Old and New Mechanisms of Action". Pharmaceuticals. 6 (8): 988–1038. doi:10.3390/ph6080988. PMC 3817731. PMID 24276379.
    61. Gokare, Prashanth; Finnberg, Niklas K.; Abbosh, Phillip H.; Dai, Jenny; Murphy, Maureen E.; El-Deiry, Wafik S. (2017-08-29). "P53 represses pyrimidine catabolic gene dihydropyrimidine dehydrogenase (DPYD) expression in response to thymidylate synthase (TS) targeting". Scientific Reports. 7 (1): 9711. Bibcode:2017NatSR...7.9711G. doi:10.1038/s41598-017-09859-x. PMC 5575263. PMID 28851987.
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    66. "No Survival Benefit with Bevacizumab Maintenance in CRC".
    67. "Scientific Founder, Oncoceutics".
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