Current Research Funded
University of Southern California (USC) Norris Comprehensive Cancer Center:
Amir Goldkorn, M.D.
Assistant Professor of Medicine (Division of Cancer Medicine and Blood Disease)
USC Norris Comprehensive Cancer Center/Keck School of Medicine
Project Title: Capture and Analysis of Circulating Tumor Cells in Patients with Ewing Sarcoma
Innovation and Impact:
We propose a collaborative effort to develop a novel biomarker platform in patients with Ewing Sarcoma. The proposed studies will constitute an exciting first step towards the use of CTC in sarcoma, and will serve as the basis for a larger, federally-funded prospective trials aimed at establishing a new paradigm of CTC-guided molecularly-based, precision management in these diseases. As such, this proposal is uniquely suited to the Kure It mission and project criteria, as it “uses human subjects”, is “conducted by MD’s”, and is “focused on an underfunded cancer,” and will “lead to individualized therapeutic options for treatment”.
Jacek K. Pinski, MD, PhD
Assistant Professor of Medicine
Co-director, Prostate Cancer Research Program
USC Norris Comprehensive Cancer Center/Keck School of Medicine
Project Title: Antibody Treatment of Prostate Cancer Expressing the Luteinizing Hormone Receptor (LHR)
In the treatment of advanced PC, the response to androgen ablation therapy is often dramatic but transient. Over time, PC cells develop castration resistance. High intratumoral androgen levels and androgen receptor (AR) activity have been described in PC cells despite the low levels of circulating androgens resulting from androgen deprivation therapy (1-3). One potential explanation for these findings is de novo androgen synthesis. Recently, several groups have shown that PC cells are capable of producing testosterone directly from cholesterol (4-6). Up-regulation of genes and proteins encoding the necessary steroidogenic enzymes has been observed during castration resistant PC (CRPC) progression (6). Although up-regulation of steroidogenic enzymes has been described in CRPC, the regulation of this androgen synthesis is poorly understood.
UCLA Jonsson Comprehensive Cancer Center
Noah Federman, MD
University of California Los Angeles
Project Title: Targeting the P13KL-AKT-mTOR pathway in pediatric bone and soft tissue sarcomas: Translating a targeted therapeutic from bench to bedside
Bone and soft tissue sarcomas are a heterogeneous group of malignancies that although rare are one of the most common cancers in children while having one of the worst prognoses overall. Furthermore, the research field of childhood sarcomas is one of the most underfunded in the cancer research field as a whole. Despite advances in current non-targeted chemotherapies the survival has plateaued for these aggressive malignancies, and we have made no progress in the treatment of metastatic sarcomas with an overall 5 year survival of about 20%. There is a dire need for development of new targeted therapeutics in these cancers, which would be applicable across the age groups from children to adults.
Dr. David Shackelford
Department of Molecular and Medical Pharmacology
University of California Los Angeles
Project Title: Therapeutically targeting oxidative stress in LKB1/STK11 deficient lung cancer
Currently there are few effective, targeted therapies for the treatment of non-small cell lung cancer (NSCLC) and no effective strategies for the prevention of lung cancer. The LKB1/STK11 tumor suppressor gene is frequently mutated in both NSCLC, and to date there are no targeted therapies for patients with LKB1 mutations. LKB1 is a serine/threonine kinase that functions as a tumor suppressor regulating growth, metabolism and mitochondrial homeostasis through the adenosine monophosphate activated kinase (AMPK) and Unc1 like kinase 1 (ULK1) pathways. Recent studies have shown that loss of LKB1 predisposes NSCLC tumor cells and hematopoietic stem cells to mitochondrial defect resulting in high levels of reactive oxygen species (ROS) and my lab has recently discovered that the oxidative stress response (OSR) is highly unregulated in human and murine LKB1 deficient lung tumors across multiple tumor subtypes including ADC and SQCC leads to elevated levels of NAD(P)H:quinone oxidoreductase (NQ01), a key effector of the OSR.
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.
Assistant Professor of Medicine and Genetics
University of North Carolina, Chapel Hill, NC
Defining the RCC kinome for target discovery and individualized therapy
Dr. William Kim is an Assistant Professor of Medicine and Genetics in the Division of Hematology / Oncology as well as member of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill. Dr. Kim received his MD degree from Brown University and completed his medical residency and oncology fellowship at the Beth Israel Hospital and Dana-Farber Cancer Institute (Harvard Medical School) respectively. A medical oncologist by training, Dr. Kim specializes in the treatment of patients with renal cell carcinoma (RCC) and runs a research laboratory focused on understanding the functional consequences of genetic and epigenetic events in RCC.
"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
Dr. James W. Mier is a graduate of Indiana University School of Medicine. He was a Clinical Associate in the NCI Medicine Branch and Laboratory of Tumor Cell Biology, where he worked under the direction of Dr. Robert C. Gallo on the isolation and characterization of Interleukin-2 (IL-2). After leaving the NCI, he spent several years in the Hematology-Oncology Division at Tufts Medical Center in Boston, where he continued his work on IL-2 as a form of immunotherapy for patients with renal cell carcinoma and melanoma. In 1997, he moved to the Beth Israel Deaconess Medical Center, where he is currently an Associate Professor in the Division of Hematology-Oncology. His laboratory research is currently focused on the various mechanisms by which renal cell carcinomas develop resistance to VEGF-targeted therapies. He is a Co-Leader of three projects in the DF/HCC Skin and Kidney Cancer SPOREs.
"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.
Kure It will again partner with the AACR to award $250,000.00. The Kure It - AACR Grant for Kidney Cancer Research represents a joint effort to promote and support innovative cancer research. As the cosponsor and grant administrator, the AACR will conduct a competitive grant application process. The grant will be awarded to a project that demonstrates innovative translational research designed to improve the survival and quality of life for patients with kidney cancer, leads to individualized therapeutic options for treatment, or focuses on the development of promising new cancer therapeutics for kidney cancer. More information about the grant opportunity and materials for applying for this award are available on proposalCENTRAL and on the AACR research funding site. The application deadline for the 2014 cycle was December 4, 2013.
• Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells
• Cancer is caused by both external factors (tobacco, infectious organisms, chemicals, and radiation) and internal factors (inherited mutations, hormones, immune conditions, and mutations that occur from metabolism)
• Most cases occur in adults who are middle-aged or older
• About 77% of all cancers are diagnosed in persons 55 years and older