2010 UALC
Katerina Politi, PhD
Yale University
Research Project:
Uncovering New Mechanisms of Resistance to Targeted Therapies using Mouse Models of EGFR Mutant Lung Adenocarcinoma
Summary:
Many lung cancer patients who have mutations to the EGFR gene initially respond well to EGFR-targeted therapies; unfortunately, patients can quickly develop resistance to this therapy. In 50% of cases, patients develop an additional mutation to the EGFR gene (T790M) that causes resistance. To find ways to overcome this resistance, Dr. Politi will be using preclinical research models engineered with these specific mutations. These models will receive the same treatment regimen as patients in a concurrent clinical trial. Using this strategy, Dr. Politi will be able to assess how the models respond to the drugs and the mechanisms underlying drug resistance, and be able to determine the relevance of her findings to patients treated with these drugs.
More Content:
Final Report
Dr. Politi has 1) established both murine and cell line models of afatinib+cetuximab resistance, 2) identified possible mechanisms of resistance that are currently being tested, 3) collected human afatinib+cetuxiamb resistant specimens for analysis. This work has set the foundation for detailed studies of how tumors become resistant to afatinib+cetuximab and is actively being pursued by her lab in collaboration with Dr. William Pao. Moreover, they have begun experiments to test whether this combination used in the front-line setting in EGFR mutant lung cancer can delay the emergence of drug resistance and are planning a clinical trial of these agents in patients with TKI-naïve EGFR mutant lung cancer.
Notable Accomplishments
Dr. Valentina Pirazzoli, a postdoctoral fellow working under Dr. Politi, received $70,000 through a post-doctoral fellowship from the American-Italian Cancer Foundation to continue work directly related to the UALC project. In addition, Dr. Politi is collaborating with Dr. William Pao to follow this research in a $1,500,00 award from the NIH. Dr. Politi published her research in Cancer Discovery and Cancer Cell. Dr. Politi has also been instrumental in an increased focus on lung cancer research at Yale, and is currently the Principal Investigator of the Yale site in the Lung Cancer Mutation Consortium, a nation-wide effort to perform lung cancer mutation testing and pair patients to clinical trials of targeted agents most likely to benefit them.