The AACR-Amgen Inc. Fellowships in Clinical/Translational Cancer Research are open to postdoctoral and clinical research fellows working at an academic, medical or research institution who will be in the first five years of their postdoctoral training at the start of the grant term. Proposed research projects may be in any area of clinical and/or translational cancer research.
Kara N. Maxwell, M.D., Ph.D.
Fellow, University of Pennsylvania, Philadelphia, PA
Identification of Clinically Relevant Breast Cancer Susceptibility Variants
"Approximately 70 percent of familial breast cancer cases are not due to mutations in the BRCA1 and BRCA2 genes. While a number of moderate risk genes have been implicated in breast cancer susceptibility, there is currently insufficient data to recommend for or against screening and prevention measures for the vast majority of these genes. However, given the increasingly widespread availability of clinical next generation sequencing, an increasing number of patients will undergo genetic testing for these moderate penetrance breast cancer susceptibility genes. While it is the hope that the decreases in morbidity and mortality seen with screening and prevention strategies in BRCA1 and BRCA2 carriers can be replicated in women carrying mutations in other genes, much research remains to be done to translate these genetic findings into safe clinical practice.
"With this award, I propose to characterize the frequency and type of variants in moderate penetrance breast cancer susceptibility genes in high risk breast cancer patient populations and to pilot studies to assess functional significance of these variants. It is my hope that these studies will provide critical data on the frequency, type and functional significance of mutations in a panel of breast cancer susceptibility genes in high risk women. The data used from this study will allow the design of a number of future clinical trials, including ethics trials involving disclosure of such genetic results and prospective trials to follow the clinical course of patients identified with mutations in moderate penetrance genes. Eventually, trials may be designed which investigate whether more intensive screening leads to a reduction in breast cancer incidence in patients with mutations in moderate penetrance genes.
"I am humbled to be chosen for the AACR-Amgen Inc. Fellowship in Clinical/Translational Cancer Research among what I am confident was an impressive pool of applications. This fellowship will allow critical research time and training to allow me to pursue a career as an independent investigator in translational cancer genetics. I am deeply grateful to my scientific mentors Dr. Katherine Nathanson and Dr. Susan Domchek for their support and guidance, and to the amazing crew of laboratory and clinical researchers within the MacDonald Family Cancer Risk Evaluation Program and Basser Center for BRCA at the University of Pennsylvania."
Victoria E. Wang, M.D., Ph.D.
Fellow, University of California, San Francisco, San Francisco, CA
The Role of the c-Met/HGF Pathway in Drug Resistance and Metastasis
"Although molecular therapies that target specific oncogenic mutations have revolutionized cancer treatment, the emergence of drug resistance and the systemic spread of tumor cells have limited our ability to eradicate cancer. Recently, several studies have implicated the c-Met/HGF pathway in metastasis and as a general mechanism in mediating resistance to tyrosine kinase inhibitors across multiple tumor types including lung, gastric and AML. Lung cancer was chosen as a platform to interrogate the role of this pathway in drug resistance and in metastasis since it remains the leading cause of cancer mortality worldwide. c-Met overexpression in lung cancer is associated with worse outcome and inhibition of this pathway improves survival in appropriately selected patients in phase II studies, thus supporting its role in tumorigenesis. A genome-wide shRNA screen has been performed to identify novel mediators of c-Met resistance. In addition, we will explore whether the c-Met/HGF pathway can induce EMT leading to innate drug resistance and enhanced metastatic potential in vitro and in vivo. These studies will hopefully lead to improved therapies augmenting responses to current c-Met inhibitors, inform clinical trial design, and ultimately improve survival not only for lung cancer patients but also patients with other c-Met driven malignancies.
"I feel deeply honored to have received the AACR-Amgen Inc. Fellowship in Clinical/Translational Cancer Research. This award will provide valuable protected time and resources for completing this project. I am greatly indebted for the continued scientific guidance of my former advisor Dr. Phil Sharp and current mentors Drs. Frank McCormick and Jeff Settleman. In addition, I am grateful for the support and translational insight of my clinical mentors, Drs. C. Babis Andreadis and Matthew Gubens, and our wonderful collaborators at the RNAi Consortium of the Broad Institute."
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