2010 UALC
Heidi Greulich, PhD
Dana-Farber Cancer Institute
Research Project:
Functional analysis of somatic mutations in lung cancer
Summary:
Molecularly-targeted therapies have proven more effective than standard chemotherapy in the treatment of lung cancer. In many cases, genes activated by a specific mutation have shown to be effective therapeutic targets. While a number of these genes are known (for example EGFR), there remain a number of unknown mutations that have potential to be effective targets. Dr. Greulich and colleagues have identified a number of genes mutated in lung adenocarcinoma. This project will functionally analyze a significant number of these mutations to confirm whether they are oncogenic, gain-of function mutations, which will in turn lead to selection of potential targets to develop new cancer drugs.
More Content:
Final Report
Dr. Greulich has tested a number of candidate oncogenes, including novel but rare mutations that are potentially clinically actionable, such as ERBB2 (HER2). Extracellular domain mutations of ERBB2, found in 1-2% of lung and breast cancers, are oncogenic and drug-sensitive. Dr. Greulich assessed how these mutations to ERBB2 affected response to certain ERB family-targeted drugs including neratinib, afatinib, lapatinib, and trastuzumab, is further investigating the mechanism by which these mutations affect cell growth, and is developing strategies for therapeutic intervention. This information will better inform rational drug design for patients whose tumors harbor ERBB2 mutations, including lung and other cancers.
Notable Accomplishments
Dr. Greulich has received over $525,000 in following funding from a grant from the Department of Defense, entitled “Functional analysis of somatic mutations in lung cancer”. Dr. Greulich published her work on ERBB2 in the Proceeding of the National Academy of Sciences.