Mutation that drives NSCLC also found in one-quarter of small cell lung cancers

Significant new treatments are available or in clinical trials for non-small cell lung cancer (NSCLC). However, the same explosion in treatment options is not true for its cousin, small cell lung cancer, a less common and more aggressive form of the disease. Results presented at the American Association for Cancer Research (AACR) Annual Meeting 2015 in Philadelphia, Pennsylvania, show the presence of a known mutation for NSCLC in small cell lung cancer, implying that promising treatments in development for NSCLC may be applicable to the other form of the disease as well.

"There is an unmet need in small cell lung cancer. There have been no significant new therapies developed in 20 years," said Fred R. Hirsch, MD, PhD, associate director for international programs at the University of Colorado Cancer Center in Aurora and CEO of the International Association for the Study of Lung Cancer.

One promising new strategy in the treatment of NSCLC is the inhibition fibroblast growth factor receptor (FGFR), which helps to signal uncontrolled, cancerous growth in approximately 21% of NSCLCs. Results presented by Hirsch and colleagues at AACR 2015 show positivity for FGFR1 amplification, mRNA, and/or protein expression in 17 of 75 patient samples (22.7%) of small cell lung cancer tumors.

"The presence of FGFR1 as a driver mutation in small cell lung cancer implies that we could repurpose drugs that target this amplification in non-small cell lung cancer for the small cell form of the disease," Hirsch said.

Small cell lung cancer accounts for 10% to 15% of all lung cancers, with 5-year survival rates less than half that of NSCLC. Because small cell lung cancer shows symptoms much later than NSCLC, it is usually diagnosed much later in the course of the disease, commonly after it has metastasized to other parts of the body, and thus many patients die within weeks or months of diagnosis.

The study identifies a subset of patients with small cell lung cancer with potentially over-activated FGFR1 pathways as evidenced by FGFR1 gene amplification, increased FGFR1 mRNA levels, and high protein expression.

"This clearly demonstrates that FGFR1 is important in a subgroup of small cell lung cancers. I would say this will lead to a clinical trial of drugs targeting FGFR in small cell lung cancer," Hirsch said. "The progress of existing drugs targeting FGFR1 means that we could be much closer to offering treatment options to people with small cell lung cancer than if we had been forced to start with a new compound."

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