Ongoing Search for Driver Mutations in Lung Cancer

Joan H. Schiller, MD


June 18, 2012

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Hello. I am Dr. Joan Schiller, Professor and Chief of the Division of Hematology and Oncology, and Deputy Director of the Simmons Cancer Center, at the University of Texas Southwestern Medical School in Dallas, Texas. Welcome to this edition of Medscape Oncology Insights, coming from the 2012 annual meeting of the American Society for Clinical Oncology (ASCO®). I am pleased to announce that this is the first in a series of commentaries produced in cooperation between Medscape and the University of Texas Southwestern.

Today I would like to talk about the molecular testing of lung cancer. Molecular testing is already in place for many types of cancers, including lung cancer. For example, we know that many patients with lung cancer have driver mutations such as EGFR and ALK. We also know that patients treated with appropriate drugs, in this case erlotinib and crizotinib, respectively, often have dramatic responses and improved survival. The problem is that those 2 mutations only represent a small minority of lung cancers.

Several years ago, a group of 14 institutions banded together to find more driver mutations that are actionable in lung cancer, the goal being to find driver mutations that we can target with drugs and induce the same dramatic responses and improved outcomes. The Lung Cancer Mutation Consortium (LCMC) is led by Paul Bunn at the University of Colorado. About 1200 patients with stage IV adenocarcinoma of the lung consented to have their tumors collected and analyzed.

Usable tumors and data were obtained from about 1000 of these patients, and mutations were found in 54%.[1]Of those, KRAS represented about 23% of all the mutations, EGFR about 20%, and EML4-ALK about 10%. The remainder 1%-2% were PI-3 kinase, RAS-1, RET, MEC, MET, AKT, BRAF, and HER2. So, that means that in about 45% of patients, we were not able to identify a targetable mutation. Therefore, the LCMC initiative continues. We are still collecting tissues.[2]We plan to collect about another 1000 adenocarcinomas and hope to extend the data collection to squamous cell carcinoma. The goal is to discover even more actionable mutations. Because many of these mutations will be very rare, we will need to collect a large number of tumors.

In the future, we want to be able to have a physician order genomic testing on a patient's lung cancer and have it come back with appropriate mutations identified so that we can target the right drug to the right patient. Thank you for joining me for this edition of Medscape Oncology Insights. This is Joan Schiller at ASCO® 2012, signing off for Medscape Oncology and University of Texas Southwestern.


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