An international team of researchers, led by investigators at the Max Planck Institute in Cologne, Germany, have reported that the fibroblast growth factor receptor-1 (FGFR1) gene is amplified in a substantial proportion of squamous non-small cell lung cancers (NSCLC).
Moreover, the investigators found that an FGFR1 inhibitor shrank tumors in xenograft models that carried the gene amplification.
The study, published in the December 15 issue of Science Translational Medicine, likely has important clinical implications.
Thus far, researchers have identified two therapeutic targets in NSCLC, EGFR mutations and EML4-ALK gene fusion. However, both of those genetic alterations are, by and large, restricted to adenocarcinomas.
By contrast, the FGFR1 amplification appears to be largely restricted to smoking-related squamous cell cancers.
For example, when the team used FISH to examine 153 squamous cell tumor samples, they found that 34 (22%) had FGFR1 amplification, whereas a SNP analysis of 581 adenocarcinoma tumors revealed FGFR1 amplification in just 6 (1%).
In a Perspective that accompanied the study, Nicolas C. Turner, of the Institute of Cancer Research in London, and Michael Seckl, of Imperial College in London, called the discovery “the first glimmer of hope” for patients with smoking-related NSCLC.
They note that while FGFR1 alterations have been seen in previous lung cancer studies, the frequency appeared to be low because the studies did not distinguish between adenocarcinoma and squamous cell cancers.
And they point out that while the current study focused on lung cancer, other smoking-related squamous cell cancers might also carry FGFR1 amplifications and thus respond to targeted inhibitors.
Multiple FGFR1 inhibitors are in preclinical development and two inhibitors—BGJ398 and AZD4547—are already in Phase I clinical trials.
And interestingly, although enrollment in the BCJ398 trial is restricted to patients whose tumors have an amplified FGFR1 or FGFR2 gene or a mutation in FGFR3, no such eligibility criteria are included in the AstraZeneca-sponsored trial of AZD4547.