al., 2004; and Pao et al., 2004) detected four EGFR mutations associated with sensitivity to gefitinib or erlotinib, and indicated that the KRAS mutation predicts a lack of response to the same drugs. Seventy-five percent of lung cancer patients with these EGFR mutations responded to tyrosine kinase inhibitors, and only 1 percent of those with the KRAS mutations responded. By comparison, clinical predictors are not as informative in predicting the likelihood of response. Nonsmoker patients, for example, have the highest response rate, but only 30 percent of nonsmokers with NSCLC respond to gefitinib or erlotinib (Table 4). There are also molecular predictors for acquired resistance to tyrosine kinase inhibitor treatment, including second-site EGFR mutations in about 50 percent of the cases, and MET amplification in about 20 percent of patients. This suggests that MET inhibitor drugs may have a role in treating patients with acquired resistance to erlotinib or gefitinib. MSKCC is starting to screen lung cancer patients for KRAS or EGFR mutations and using this information, which can be acquired from the tissue removed in a needle biopsy, to decide which patients to treat with tyrosine kinase inhibitors. In conjunction with Dr. Varmus, Drs. Kris and Pao also developed a transgenic mouse lung cancer model, with the same EGFR mutations that cause lung cancer in humans, to screen for more effective tyrosine kinase inhibitors. “This is a nice example of a mouse model using transgenic technology in order to do preclinical studies,” Dr. Mendelsohn said.

The cost of doing tumor biopsies and genomic and proteomic tests on the biopsied tissues was discussed. Drs. Kris and Pao noted that in their studies, this cost was about $5,000 per lung cancer patient. The cost was covered through grants or philanthropy and not by third-party payers. The New York researchers continue to do studies aimed at confirming the useful-