Current Research Funded
Oregon Health and Science University’s Knight Cancer Institute (OHSU):
George Thomas, M.D.
George Thomas, M.D. is an Associate Professor of Pathology and Laboratory Medicine at Oregon Health and Science University’s Knight Cancer Institute. Dr. Thomas’ laboratory works on decoding how targeted drugs work and leverages this knowledge to individualize cancer treatments. Dr. Thomas is clinically active, with subspecialty interest in genitourinary and molecular pathology. Dr. Thomas received his clinical and laboratory training at the Harvard and UCLA pathology programs. He was on the faculty at UCLA before joining OHSU. To read more about the groundbreaking work being conducted by Dr. Thomas, please Click here
The University of North Carolina, Chapel Hill, NC:
William Youngkwan Kim, M.D.
Dr. Kim is currently working on defining the RCC kinome for target discovery and individualized therapy.
"Approximately 65,000 new cases of renal cell carcinoma (RCC) occur annually in the US and its incidence is on the rise. While a number of kinase inhibitors are FDA approved for use in advanced RCC, their primary mode of action is believed to be antiangiogenic, via inhibition of the vascular endothelial growth factor receptor (VEGFR), or by inhibition of the mammalian target of rapamycin (mTOR). While sequencing of RCC has revealed inactivating mutations of tumor suppressor genes as well as genes involved in histone and chromatin modification, there is a paucity of kinase mutations. We have defined that there are three intrinsic kinomic subclasses of RCC and hypothesize that the RCC kinome, despite not being mutated, remains a tractable and actionable therapeutic target. Our work will define the activation state of the RCC kinome at the protein level and determine whether RCC kinomic subclass can predict therapeutic response to tailored kinase inhibition. The information garnered from this study should allow us to define a subset of kinases that are activated in RCC, differentiate kinomic subclasses of RCC, and lay the groundwork to begin to personalize kinase therapy based on the currently therapeutically actionable subset of the genome: the kinome."
Beth Israel Deaconess Medical Center, Boston, MA:
James W. Mier, M.D.
HDM2/HDMX as a Therapeutic Target in Renal Cell Carcinoma
"Tyrosine kinase inhibitors (TKIs) that target VEGF receptor signaling are among the drugs most frequently used in the first-line treatment of patients with renal cell carcinoma (RCC). Although treatment with these agents delays disease progression for several months in the majority of patients, it almost never induces complete responses and in those patients that respond initially, resistance inevitably develops after a few months of treatment. My laboratory has been focused on the mechanisms by which RCCs escape from VEGF-targeted treatment. One of the adaptations we have observed in RCC xenografts that have become resistant to sunitinib is the disabling of p53 function. Although the p53 gene is intact in the majority of RCC and the expression of p53-dependent genes is readily induced by treatment, these alterations in gene expression are not sustained during TKI treatment, despite the persistence of p53 levels. The concurrent administration of an HDM2 antagonist, however, results in persistent expression of p21 and other p53-dependent genes and sustained tumor non-progression. Treatment with sunitinib results in an influx of CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSC), presumably due to the induction of the chemokine SDF-1. Both SDF-1 induction and the infiltration of tumor tissue by MDSC are suppressed by HDM2 antagonists. Finally, HDM2 antagonists suppress the expression of HIF-2a, the dominant oncoprotein in VHL-deficient RCC. Collectively, these data suggest that HDM2 antagonists might be ideal adjuncts to VEGF-targeted TKIs in the management of RCC. We hope to use the funds from Kure-It/AACR grant to further define the mechanisms by which HDM2 antagonists cooperate with TKIs to limit the growth and vascularity of RCC xenografts and ultimately, to apply our findings to the design of clinical trials that test the efficacy of these drug combinations in RCC patients."
Past Research Funded
Researchers from Cedars-Sinai:
Neil Bhowmick, Ph.D.
Neil Bhowmick, PhD is an Associate Professor of Medicine and a member of the Uro-Oncology Research Program at the Samuel Oschin Comprehensive Cancer Center Institute at the Cedars-Sinai Medical Center.
Dr. Bhowmick’s laboratory studies focus on prostate cancer, including the roles of numerous agents in the disease’s growth and treatment. The research in Dr. Bhowmick’s lab is supported by the National Cancer Institute, the Department of Defense and the Veterans Administration.
After earning his bachelor’s degree from the University of Florida, Dr. Bhowmick earned his doctorate in biochemistry and molecular biology from the University of Georgia. He then completed a postdoctoral fellowship in cancer biology at Vanderbilt University Medical Center in Nashville, TN.
Hyung Lae Kim, M.D.
Hyung Lae Kim, MD is Associate Director for Surgical Research at the Samuel Oschin Comprehensive Cancer Institute, Director of Academic Programs and Associate Program Director for the urology residency program.
Dr. Kim's clinical practice focuses on treating cancers of the prostate, bladder, kidney and testis. He has extensive experience applying minimally invasive and robotic surgical techniques, and has published methods for improving the surgical management of urologic cancers. He is actively involved in developing and running innovative clinical trials that utilize novel treatment approaches.
Dr. Kim graduated with a bachelors degree from the University of Michigan before earning his medical degree from the University of Chicago's Pritzker School of Medicine. He continued his training with a residency in urology at the University of Chicago before completing two fellowships at the University of California, Los Angeles, in urologic oncology and in minimally invasive surgery. Before joining the staff at Cedars-Sinai Medical Center, Dr. Kim was Associate Professor and Vice Chair of Urology at the Roswell Park Cancer Institute in Buffalo, New York.
Researchers from City of Hope:
Sumanta Kumar Pal, M.D.
Sumanta Kumal Pal, M.D. is an Assistant Professor in the Department of Medical Oncology & Experimental Theraputics at the City of Hope Comprehensive Medical Center. He began his college career at the age of 13 through the Early Entrance Program at California State University Los Angeles. He subsequently began medical school at the age of 17 at the University of California – Los Angeles.
While attending UCLA, Dr. Pal developed an immediate interest in cancer research and began working with Dr. Dennis Slamon, studying mechanisms of resistance to the breast cancer drug trastuzumab. He carried on with these studies through the course of his residency. After completing his residence, Dr. Pal transition to City of Hope, where he trained with Dr. Robert Figlin and worked with genitourinary cancer studies.
Dr. Pal has garnered numerous awards supporting his research, including support from the California Breast Cancer Research Program, the National Comprehensive Cancer Network and the National Institute of Health. Around his year anniversary working with City of Hope, Dr. Pal had already been extremely productive, with over 40 peer reviewed publications.
Hua Yu, Ph.D.
Dr. Yu is currently a professor of Cancer Immunotherapeutics & Tumor Immunology. She is also a Full Member at Cancer Immunotherapeutics Program, Comprehensive Cancer Center. Dr. Yu’s laboratory was the first to validate STAT3, a critical regulator of tumor cell survival and proliferation, as a molecular target for cancer therapy in animal models. Yu’s team also unraveled a critical role of STAT3 in tumor angionesis and tumor immune evasion.
Dr. Yu attended Columbia University, where she obtained he Bachelor’s and PhD. She went on to get her Post Doctorate at the University of Michigan, studying molecular biology.