The AACR-FNAB Career Development Award for Translational Cancer Research is open to junior faculty in their first full-time faculty appointment. Research projects are restricted to translational cancer research focused on any individualized therapeutic area. Proposed project must have implications for individualized cancer treatment and must make use of human biopsies or samples, such as needle biopsies or circulating cancer cells. In vivo primary tumor explants meet these criteria, but xenografts from established cell lines do not.
2010 GRANTEE
Arnold I. Chin, M.D., Ph.D.Assistant Professor, The University of California, Los Angeles, Los Angeles, CA
Quantitative Molecular and Drug Sensitivity Analysis for Bladder Cancer
"It is truly an honor to receive the AACR Career Development Award for Translational Research. I am grateful to Drs. Genhong Cheng, Owen Witte and Jean deKernion for their mentorship and continued support. This award will be critical in developing the translational focus of my research program.
"Bladder cancer has high social, as well as financial, costs. In the United States, it is the fifth most common cancer, with an incidence of more than 70,000 and mortality of greater than 14,000 per year. Treatments can involve extensive surveillance and radical surgery with considerable morbidity, making it one of the most expensive cancers in the United States, estimated at $3.7 billion per year. As a surgeon and a scientist, I am in a unique position to impact the lives of those afflicted with bladder cancer.
"Numerous targeted therapies consisting of small compounds or monoclonal antibodies have been developed, although none have been approved for bladder cancer. Given the molecular heterogeneity of bladder cancer, we predict differential responses to targeted therapies. By testing the tumors of individual patients to sensitivity of known targeted agents and correlating with a specific gene array and expression profiles, we will provide the foundation to individualize treatments for bladder cancer patients and potentially improve screening of patients for clinical trials to accelerate development of novel therapies. Costs of large-scale drug sensitivity screening can be prohibitively expensive as well as prone to variation, and we will adopt a novel microfluidic device to process samples with efficiency and precision.
"We also anticipate the patient-linked tissue bank will further the molecular characterization and indexing of urothelial cell carcinoma. Included will be patients with recurrent superficial disease. Bladder cancer is fairly unique to oncology that recurrent non-invasive tumors are removed until progression dictates more radical therapy. This lends itself to studying the molecular progression of tumors within single patients and has important implications in designing individualized therapies. Ultimately, this will lead to individualized tailoring of therapeutic decisions based on an efficient, high-throughput analysis and further the understanding of genetic changes to bladder cancer progression."
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2008 GRANTEE
Tara A. McCannel, M.D., Ph.D.
Assistant Professor, University of California, Los Angeles, Los Angeles, CA
High Resolution Cytogenetic Study of Archival Metastatic Choroidal Melanoma
"The goal of Dr. Young's research is to determine if high-resolution, genome-wide patterns of cytogenetic aberration within archival, primary choroidal melanoma tissue from patients of known metastatic outcome can accurately predict metastatic risk. Choroidal melanoma, a cancer arising from within the eye, causes both blindness and death. Despite successful treatments for the eye, 50 percent of patients will die of metastasis, or spread of the cancer to other parts of the body. No treatment for this cancer has been shown to improve survival. High resolution DNA and RNA microarray analyses will be performed on archival primary choroidal melanoma tumor tissue provided by the Collaborative Ocular Melanoma tissue bank. These data will be integrated with extensive existing microarray information from patient biopsies performed at UCLA for which metastatic outcome is not yet known. Cluster analysis with respect to both monosomy 3 and clinical metastatic outcome will be performed to identify key over- and under-expressed genes for molecular studies of metastasis. The access to archival material from the Collaborative Ocular Melanoma tissue bank has the advantage of known long-term patient follow-up including extensive medical histories on these patients which include whether the patients developed cancer metastasis or not. Our research will establish the link between which molecular signatures correlate most highly with choroidal melanoma patients who ultimately develop metastatic disease. This information will be important for future patients who are diagnosed with this cancer. By knowing with greater accuracy which patients will develop metastasis, we can offer systemic therapies to help improve patient survival early in the course of the cancer. In addition, knowing the key molecular differences between patients with good-prognosis and poor-prognosis will help us learn more from a scientific level how these cancers cause metastasis. The ultimate goal of this research will be to help develop treatments and cures for patients with choroidal melanoma."
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