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Kidney Cancer Research
Research Kidney Cancer
Arie Belldegrun, MD
Dr. Belldegrun is internationally recognized in the field of surgical and medical management of urological cancers, designing and conducting large-scale clinical trials, and in the development of innovative therapies for patients with localized and metastatic kidney, bladder, and prostate cancer. Dr. Belldegrun’s research laboratory at UCLA has been a pioneer in the fields of genetic cancer therapy, immunotherapy, cancer vaccines, and targeted molecular therapy for urological malignancies.
Dr. Arie Belldegrun's research focuses on targeted specific therapy and immunotherapy of kidney and prostate cancers. Belldegrun's laboratory reported on the cloning of a tissue specific and androgen responsive novel 620 bp PSA promoter sequence and upstream sequence. The enhanced gene expression of the resulting construct, combined with its tissue specificity and androgen responsiveness, provide the foundation for the development of tissue specific vectors for prostate cancer gene therapy.
Belldegrun's laboratory also has studied the feasibility of isolating functional dentrictic cells from the peripheral blood of renal cell carcinoma patients and has compared their transduction efficiency using various methods of transferring gene markers into dentritic cells.
Jim C. Hu, MD, MPH
Jim Hu, MD, MPH is a health services researcher and the Director of Minimally Invasive and Robotic Surgery. The duality of his research and clinical experience has resulted in noteworthy comparative effectiveness research comparing new treatment modalities with traditional approaches, such as open surgery.
Additionally, Dr. Hu is internationally renown as a robotic surgeon and has published 10 papers with video demonstrations that illustrate technical modifications to improve outcomes of robotic assisted laparoscopic radical prostatectomy and robotic assisted partial nephrectomy.
Allan J. Pantuck, MD
Dr. Allan Pantuck’s research programs focus on gene and immune therapies for GU cancer, molecular and genomic characterization of kidney cancer, and nutritional chemoprevention of prostate cancer.
Funding has been received and work completed on a project to study chromosome 9p alterations in kidney cancer, a continuation of work started in Dr. Pantuck’s NIH-awarded K23 training grant, which ultimately led to publication of a manuscript in the journal Cancer. Dr. Pantuck’s work on genetic and molecular characterization of kidney cancer will now continue with a recently funded grant, for which he is the PI, from the Department of Defense titled “Early diagnosis of clear cell kidney cancer using VHL/HIF pathway regulated circulating microRNA,” which seeks to identify a novel panel of microRNAs that are measurable in serum for the early diagnosis of kidney cancer. Furthermore, Dr. Pantuck will receive funding for an NSF SBIR phase II grant with the UCLA Momentum Incubator spin-off Fibron Corporation, and will also serve as co-investigator on a recently funded, 5 year NIH-funded R01 grant on prostate cancer imaging.
For ten years, Dr. Pantuck has been collaborating with Dr. Arie Belldegrun to develop a targeted kidney cancer vaccine (AdGMCAIX). A RAID grant was successfully submitted to produce clinical grade vaccine material, and its manufacture has now been completed. A clinical trial utilizing this GMP manufactured vaccine has been approved by the FDA Recombinant Advisory Committee, and toxicology studies are being completed in support of an IND application for an investigator initiated clinical trial to be performed at UCLA. The intellectual property for AdGMCAIX has been successfully licensed to Kite Pharma. Two patent applications have been submitted to the Office of Intellectual Property, US Patent application No. 61/103,895, Genomic Predictor of Kidney Cancer Prognosis and Interleukin-2 Treatment Response and UCLA CASE NO. 2010-306: Molecular Signature to Predict Prognosis for Localized Clear Cell Kidney Cancer.
Dr. Pantuck’s research is currently funded by the National Institutes of Health, Department of Defense and the National Science Foundation.
Matthew Rettig, MD
Matthew Rettig, M.D. is an Associate Professor in the Department of Medicine, Division of Hematology-Oncology, and the Department of Urology, and is the Medical Director of the Prostate Cancer Program of the Institute of Urologic Oncology at the David Geffen School of Medicine at UCLA. After receiving his medical degree from Duke University, Dr. Rettig completed internal medicine residency at the University of Washington before going on to a hematology-oncology fellowship at UCLA.
As a medical oncologist, he focuses on the management of genitourinary malignancies with a focused clinical emphasis on advanced prostate cancer. Dr. Rettig has both a clinical and bench research program. As the director of the clinical trials program in prostate cancer at UCLA, he conducts multiple prostate cancer clinical trials that span the spectrum of the states of the disease: from neoadjuvant therapies to post-chemotherapy, castration-resistant disease. Dr. Rettig’s bench research program, which is funded by the NIH, Department of Defense and the Department of Veterans Affairs, is focused on identifying biochemical targets for therapeutic translation in castration-resistant prostate cancer and clear cell renal cell carcinoma.
Joseph Riss, Ph.D.
The main research interest for Dr. Riss, Director of Research for the UCLA Kidney Cancer Program, is immunotherapy for treating metastatic renal cell carcinoma. Metastatic renal cell carcinoma (mRCC) poses a therapeutic challenge because of its resistance to conventional modes of therapy. In the past five years, new forms of targeted molecular therapies such as Elastin and Sutent have been added to Interferon and Interleukin-2 (IL-2) as new treatments for kidney cancer. Despite these advances in targeted therapies, the long-term survival for patients with mRCC remains poor and durable cures remain rare and primarily related to the use of high dose IL-2. Furthermore, these clinical responses are obtained at the cost of substantial toxicities to patients, and with targeted therapies these toxicities have become chronic. As a result, there remains an urgent need for the development of novel, more effective but less toxic therapies for patients with mRCC. One such concept would be to develop an immune based therapy that is combined with molecularly targeted FDA approved drugs. Using in vitro and in vivo immunotherapeutic experiments, pharmacogenomic analysis, clinical data, and pathway biology, we are identifying drugs that will have synergistic efficacy with active cellular immunotherapy targeting RCC biomarkers as the tumor antigen carbonic anhydrase IX (CAIX; 1).
Cancer as Wounds That Do Not Heal: Development of Diagnostic Tools and Combination Drug Therapy to Cancer
Cancers have been described as wounds that do not heal, suggesting that the two share common features. In our recently published study (2), we compared microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), and asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.e., changed in opposite directions). The discordant gene signature revealed processes and pathways that reflect the intrinsic pathologic nature of RCC. Using pharmacogenomic analysis, pathway biology, drug screening and in vivo experiments, we are interested to identify drugs and therapies that will recognize and/or regulate the pathways and genes that are discordantly expressed in RRR and RCC. Therefore, these drugs are expected to target renal tumors while sparing the normal regenerating kidney (3, 4).
References:
1) Hernandez JM., et al., Novel kidney cancer immunotherapy based on the granulocyte-macrophage colony-stimulating factor and carbonic anhydrase IX fusion gene. Clin Cancer Res. 2003 9 (5): p.1906-16.
2) Riss, J., et al., Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma. Cancer Res. 2006. 66(14): p. 7216-24.
3) Potter JD., Morphogens, morphostats, microarchitecture and malignancy. Nature Cancer Reviews, 2007. 7(6): 464-474.
4) Schafer M and Werner S, Cancer as an overhealing wound: an old hypothesis revisited. Nature Reviews Molecular Cell Biology, Vol. 9 (8): 628-38.
Significant breakthroughs include: 1) Development of an animal model in Blab\C mice for GMCSF-CAIX immunotherapy against kidney cancer; 2) Discovery of the discordant genes between kidney cancer and wound healing and their translational usage; 3) HIFs pathway, writing the molecular interaction map and its first in silico simulation; 4) Participated in the understanding of the role of hypoxia-inducible factors 2a ( HIF2a) in cancer; 5) Participation in the development of novel bioinformatics tools (NCI\NIH Miner’s suit); 6) Discovery of OCT1 isoforms.
Christopher Saigal, MD, PhD
Dr. Christopher Saigal’s research is focused on the nexus of quality of care and trends in medical technology. The Urologic Diseases in America project, an ongoing, NIH-funded research enterprise, evaluates quality, cost, and technology trends in major urologic conditions such as prostate, kidney and bladder cancer, as well as benign diseases such as benign prostatic hyperplasia and kidney stones. Over 60 policy-relevant manuscripts have resulted from this project. Other major research efforts involve finding ways to use technology to improve decision making for patients in the setting of localized prostate cancer. Specifically, this research tests ways to improve “shared decision making” using computer applications. Dr. Saigal also leads the UCLA site for two national NCI-funded trials to examine outcomes of care in men treated for localized prostate cancer.
Dr. Saigal’s research is currently funded by the National Institutes of Health, National Cancer Institute and the Lance Armstrong Foundation.
