this project aims to establish a Lung Cancer Mutation Consortium (LCMC) consisting of 13 institutions with a major interest in lung cancer and genomic testing of lung cancer as documented by having major NCI grants in lung cancer. The LCMC members will collect linked clinical, pathologic and genomic data on 1000 patients with advanced adenocarcinoma of the lung in the proposed clinical trial. The genomic tests will be conducted in CLIA certified laboratories located at consortium institutions according to consortium protocols. The protocol will determine the frequency of each genetic change;the association between the genetic change, the clinical features, and the outcome;and the association between different genetic changes. The information will be used to validate and/or change the pathologic sub-classification of adenocarcinomas. The genetic analyses will be used to determine if patients with specific genetic changes are eligible for enrollment into therapeutic trials evaluating novel targeted therapies directed at the specific mutation / amplification / fusion gene. These therapeutic trials are funded by other mechanisms. The proposal will lead to the creation of at least 16 new positions and to the purchase of equipment and reagents for the genetic testing. The trial results and the establishment of the LCMC will hasten the implementation of personalized medicine for lung cancer.
Relevance Lung cancer is the leading cause of cancer death in men and women in the U.S., accounting for about 30% of all cancer deaths. About half of all lung cancer patients present with advanced disease for which standard chemotherapy combinations produce only modest survival improvement with the associated high toxicity rates, inconvenience of intravenous administration and high costs. Recent molecular studies showed that as many as 50% of lung cancer have activating mutations in known oncogenes to which novel therapeutic agents have been developed. Early clinical trials suggest that targeted oral agents have less toxicity and greater benefit than chemotherapy but only when administered to patients with the specific mutated oncogene. The new technologies in this application will allow a large number of lung cancer patients to have molecular tests for these newly described oncogenes so that we can understand their frequency, relevance and importance as predictors to benefit from the new targeted agents. This proposal will hasten the development of personalized medicine for lung cancer and other cancers as well.
|Pillai, Rathi N; Behera, Madhusmita; Berry, Lynne D et al. (2017) HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium. Cancer 123:4099-4105|
|Li, Bob T; Ross, Dara S; Aisner, Dara L et al. (2016) HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers. J Thorac Oncol 11:414-9|
|Noonan, Sinéad A; Berry, Lynne; Lu, Xian et al. (2016) Identifying the Appropriate FISH Criteria for Defining MET Copy Number-Driven Lung Adenocarcinoma through Oncogene Overlap Analysis. J Thorac Oncol 11:1293-1304|
|Villaruz, Liza C; Socinski, Mark A; Abberbock, Shira et al. (2015) Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium. Cancer 121:448-56|
|Sholl, Lynette M; Aisner, Dara L; Varella-Garcia, Marileila et al. (2015) Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience. J Thorac Oncol 10:768-777|
|Kris, Mark G; Johnson, Bruce E; Berry, Lynne D et al. (2014) Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311:1998-2006|
|Rudin, Charles M; Hong, Kelvin; Streit, Michael (2013) Molecular characterization of acquired resistance to the BRAF inhibitor dabrafenib in a patient with BRAF-mutant non-small-cell lung cancer. J Thorac Oncol 8:e41-2|
|Ohashi, Kadoaki; Sequist, Lecia V; Arcila, Maria E et al. (2013) Characteristics of lung cancers harboring NRAS mutations. Clin Cancer Res 19:2584-91|
|Chaft, Jamie E; Arcila, Maria E; Paik, Paul K et al. (2012) Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling. Mol Cancer Ther 11:485-91|
|Cardarella, Stephanie; Ortiz, Taylor M; Joshi, Victoria A et al. (2012) The introduction of systematic genomic testing for patients with non-small-cell lung cancer. J Thorac Oncol 7:1767-74|
Showing the most recent 10 out of 13 publications