KRAS Mutations In Lung Cancer Predict Poor Response To Kinase Inhibitors

NEW YORK (Reuters Health) - Lung adenocarcinomas with activating mutations in the KRAS gene demonstrate poor sensitivity to the kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva), new research indicates. Coupled with past research, this finding could lead to more individualized therapies for lung cancer.

Up to 30% of lung adenocarcinomas are known to contain KRAS mutations, lead author Dr. William Pao, from Memorial Sloan-Kettering Cancer Center in New York, and colleagues note. However, the effect of these mutations on the response to gefitinib and erlotinib was unclear.

Previous reports have shown that mutations in the gene for the epidermal growth factor receptor (EGFR) are associated with sensitivity to the kinase inhibitors. Given that KRAS works downstream from EGFR, it was possible that KRAS mutations might also influence drug sensitivity.

Dr. Pao's team screened 60 lung adenocarcinomas for mutations in KRAS and EGFR and tested tumor sensitivity to gefitinib and erlotinib. While EGFR mutations predicted sensitivity to these drugs, KRAS mutations predicted a lack of sensitivity, according to their report in PLoS Medicine, published online January 24th.

"Our findings indicate that if you have a KRAS mutation, the chance of tumor shrinkage with these drugs is basically zero," Dr. Pao told Reuters Health.

Interestingly, KRAS and EGFR mutations are seldom found together in the same tumor, Dr. Pao noted. Combined with previous research, "our findings suggest that testing for mutations in both could help determine when a patient is likely to respond to gefitinib and erlotinib."

Larger studies are needed to confirm the present findings, but Dr. Pao believed that KRAS and EGFR mutation testing could play an important role in treatment algorithms. He added that his group is currently working "on getting a rapid test for KRAS mutations."

Source: PLoS Medicine 2005;2:e17. [ Google search on this article ]

MeSH Headings: Membrane Proteins : Receptors, Cell Surface : Receptor, Epidermal Growth Factor : Receptors, Gastrointestinal Hormone : Receptors, Growth Factor : Receptors, Peptide : src-Family Kinases : Receptor Protein-Tyrosine Kinases

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