David Cheresh, Ph.D.
- Distinguished Professor, Vice-Chair for Research and Development
- Associate Director for Translational Research, Moores UCSD Cancer Center
- Solid Tumor Therapeutics Program
- Ph.D. - University of Miami, 1982
Tumor growth, invasion, stem cells and drug resistance. Molecular regulation of tumor growth and angiogenesis. Drug development targeting molecular pathways involved in tumor growth metastasis and angiogenesis.
The Cheresh laboratory focuses on the discovery of molecular pathways involved in the progression of cancer. Cheresh’s earlier work identified integrin αυβ3 as a biomarker of tumor angiogenesis and tumor progression. He was involved in the discovery of a drug called cilentigide which targets integrins αυβ3 and αυβ5. This drug is being clinically developed by Merck-Serono and has shown significant survival activity in patients with Glioblastoma. Depending on the outcome of a recently completed Phase III trial, cilengitide could be the first integrin antagonist to be approved for use in oncology.
The Cheresh laboratory has identified a series of critical microRNAs that regulate the growth of blood vessels. These microRNAs control the angiogenic switch that occurs during the earliest stages of tumor growth and neovascularization in the retina. As such one of these microRNAs may have therapeutic application as it is capable of maintaining blood vessels in the quiescent state.
Cheresh and colleagues have identified integrin αυβ3 as a biomarker of tumor stem cells during intrinsic or acquired resistance of a wide range of tumors including: cancer of the lung, pancreas, breast, and colon. Cheresh and his lab discovered that αυβ3 expression is both necessary and sufficient to account for tumor stemness and drug resistance based on its ability to drive a molecular pathway regulating these processes. This has lead to the development of new therapeutic strategies to resensitize patients to drugs such as erlotinib and lapatinib that target EGFR.
The Cheresh laboratory has identified RAF kinase as an important target involved in tumor growth and angiogenesis. They have developed a new drug design strategy to target RAF and other relevant kinases by designing allosteric inhibitors of these targets. This is based on the use of defined chemical scaffolds to dock into an allosteric pocket on these kinases to render them inactive. The combined use of in silico and biological screening has yielded drugs with nM anti-tumor activity that produce strong anti-tumor growth in mouse models following once a day oral dosing. This approach appears to yield drugs that target tumors that are resistant to ATP mimetic inhibitors of RAF, Kit or PDGFR.
- Hood, J.D, Bednarski, M, Frausto, R, Guccione, S, Reisfeld, R.A, Xiang, R. & Cheresh D.A. Tumor regression by targeted gene delivery to the neovasculature. Science 2002; 296:2404-7
- Alavi, A, Hood, J.D, Frausto, R, Stupack, D.G. & Cheresh D.A. Role of Raf in vascular protection from distinct apoptotic stimuli. Science 2003; 301:94-6
- Weis, S.M. & Cheresh D.A. Pathophysiological consequences of VEGF-induced vascular permeability. Nature 2005; 437:497-504
- Stupack, D.G, Teitz, T, Potter, M, Mikolon, D, Kidd, V.J, Lahti, J.M. & Cheresh D.A. Potentiation of neuroblastoma metastasis by loss of caspase 8. Nature 2006; 439:95-9
- Murphy, E.A, Majeti, B.K, Barnes, L, Makale, M, Weis, S.M, Wrasidlo, W. & Cheresh D.A. Nanoparticle mediated drug delivery to tumor vasculature suppresses metastasis. Proc Natl Acad Sci USA 2008; 105:9343-8, PMCID2453735
- Greenberg, J.I, Shields, D.J, Barillas, S.G, Acevedo, L.M, Murphy, E, Huang, J, Scheppke, E, Stockmann, C, Johnson, R.S, Angle, N. & Cheresh D.A. A role for VEGF as a negative regulator of pericyte function and vessel maturation. Nature 2008; 456: 809-13, PMCID2605188
- Desgrosellier, J.S, Barnes, L.A, Shields, D.J, Huang, M, Lau, S.K, Prévost, N, Tarin, D, Shattil, S.J. and Cheresh D.A. Integrin avb3/c-src “Oncogenic Unit” Promotes Anchorage-independence and Tumor Progression. Nature Medicine 2009; 15:1163-1169, PMCID2759406
- Shields, D.J, Niessen, S, Murphy, E, Mielgo, A, Desgrosellier, J.S, Lau, S.K, Barnes, L.A, Lesperance, J, Bouvet, M, Tarin, D, Cravatt, B.F, & Cheresh D.A. RBBP9: A tumor-associated serine hydrolase activity required for pancreatic neoplasia. Proc Natl Acad Sci USA. 2010 Feb 2; 107(5):2189-94, PMCID2836678
- Anand, S, Majeti, B.K, Acevedo, L.M, Murphy, E.A, Mukthavaram, R, Scheppke, L, Huang, M, Shields, D.J, Lindquist, J.N, Lapinski, P.E, King, P.D, Weis, S.M. and Cheresh, D. A. MicroRNA-132 mediated loss of p120RasGAP activates endothelium to facilitate pathological angiogenesis. Nature Medicine 2010; 6:909-14, PMCID3094020
- Mielgo, A., Seguin, L., Huang, M., Camargo, M.F., Anand, S., Franovic, A., Weis, S.M., Advani, S.J., Murphy, E. and Cheresh, D.A. A MEK-independent role for CRAF in mitosis and tumor progression. Nature Medicine 2011; 17(12): 1641-45, PMC3233644
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Dr. Cheresh is Professor and Vice Chairman of Pathology at Moores UCSD Cancer Center, University of California, San Diego. He is also Associate Director for Translational Research at the Moores UCSD Cancer Center. Prior to relocating his laboratory in 2005, Dr. Cheresh was a professor in the Departments of Immunology and Vascular Biology at The Scripps Research Institute, focusing on the role of adhesion receptors and growth factors in the angiogenesis of tumors.
Dr. Cheresh received his doctorate in Immunology from the University of Miami in Florida. In 1982 he joined The Scripps Research Institute as a postdoctoral fellow in the Department of Immunology. He was promoted to Assistant Professor in 1985 and to Professor in the Departments of Immunology and Vascular Biology in 1996. Dr. Cheresh is the recipient of several awards including the 15th Hans Linder Memorial Lecture from the Weizmann Institute of Science in Rehovot, Israel, the XXIII Annual Myron Karon Memorial Lectureship from the University of Southern California, the Robert Flynn Professorship Award from Tufts University School of Medicine, and he was a recipient of The American Cancer Society Faculty Research Award and a Merit Award from the National Institutes of Health. He currently serves as Associate Editor for several major scientific journals and is on the advisory board of several others. He has been a member of the Pathobiochemistry Study Section of NIH, and currently is Chairman on the Scientific Advisory Board for the Keystone Symposia.
Dr. Cheresh continues to be a prolific researcher and scientist in the fields of cancer, vascular biology and angiogenesis. Dr. Cheresh also works with a number of firms developing angiogenesis-related drug therapies.Click here to contact me
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