Using of antifolates in NSCLC subtype treatment
According to results of a recent study patients with non-small cell lung cancer who have mutations in the KRAS gene should respond well to the antifolate class of drugs. The study made by Quintiles compared human lung cancer cell lines and patients.
The lead researcher Sarah Bacus, Ph.D., Quintiles senior vice president and chief scientific officer of translational research and development, oncology, said:
"Our study shows that when people with lung cancer have certain changes in the KRAS gene, they become exposed to antifolate drugs. This treatment keeps the KRAS gene from being expressed in cancer cells and they die, because they depend on this gene."
KRAS mutant non-small cell lung cancer (NSCLC) is an "aggressive form" of cancer. Until today, there have been limited treatment options for these patients.
Bacus and colleagues treated human NSCLC cell lines (KRAS wild type, KRAS mutant nonamplified and KRAS mutant amplified) with the antifolates methotrexate or pemetrexed.
The researchers discovered that KRAS wild-type and KRAS mutant amplified cells were relatively resistant to antifolate treatment. In contrast, antifolates inhibited growth in KRAS mutant nonamplified cell lines. The researchers also discovered a potent down regulation of KRAS gene expression in treated cells. Bacus reported dramatic and prolonged responses to pemetrexed therapy in patients with KRAS mutant NSCLC.
Bacus recommended that oncologists order 2 tests: one looking for the KRAS mutation and the other to measure KRAS amplification. Cancer mutations is not enough, we should look at gene copies. It is important before taking very expensive drugs to make sure that these mutations appear.
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