Antifolates Show Promise Against NSCLC Subtype
November 13, 2011
- Aggressive lung cancers harboring KRAS mutations are sensitive to antifolates.
- Antifolates decrease KRAS gene expression.
- Large clinical trials needed to investigate antifolate effects in cancers with respect to driving mutations.
SAN FRANCISCO — Patients with non-small cell lung cancer who have mutations in the KRAS
gene should respond well to the antifolate class of drugs, according to results of a recent study conducted by Quintiles comparing human lung cancer cell lines and patients.
“Our findings indicate that when patients with lung cancer have specific changes in the KRAS
gene, they become very amenable to antifolate drugs,” said lead researcher Sarah Bacus, Ph.D., Quintiles senior vice president and chief scientific officer of translational research and development, oncology. “This treatment stops the KRAS
gene from being expressed in cancer cells and they die because they depend on this gene.”
Bacus presented the study results at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, held Nov. 12-16, 2011.KRAS
mutant non-small cell lung cancer (NSCLC) is an “aggressive form of cancer,” Bacus said. “Until today, there have been limited treatment options available for those 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.
Results showed 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 downregulation of KRAS
gene expression in treated cells. Bacus reported dramatic and prolonged responses to pemetrexed therapy in patients with KRAS
Bacus recommended that oncologists order two tests: one looking for the KRAS
mutation and the other to measure KRAS
amplification. “Looking at the cancer mutations is not enough; you have to look at gene copies,” Bacus said. “It is important before administering very expensive drugs to make sure that those mutations appear.”
This study was funded by the Quintiles Translational Research and Development Group; no external funding was used to finance the research.
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