Antifolates Show Promise Against NSCLC Subtype
- 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 mutant NSCLC.
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.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 laboratory, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards to young investigators, and it also funds cutting-edge research projects conducted by senior researchers. The AACR has numerous fruitful collaborations with organizations and foundations in the U.S. and abroad, and functions as the Scientific Partner of Stand Up To Cancer, a charitable initiative that supports groundbreaking research aimed at getting new cancer treatments to patients in an accelerated time frame. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care, and Educational Workshops are held for the training of young cancer investigators. The AACR publishes seven major peer-reviewed journals: Cancer Discovery; Cancer Research; Clinical Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Prevention Research. In 2010, AACR journals received 20 percent of the total number of citations given to oncology journals. The AACR also publishes Cancer Today, a magazine for cancer patients, survivors and their caregivers, which provides practical knowledge and new hope for cancer survivors. A major goal of the AACR is to educate the general public and policymakers about the value of cancer research in improving public health, the vital importance of increases in sustained funding for cancer research and biomedical science, and the need for national policies that foster innovation and the acceleration of progress against the 200 diseases we call cancer.
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