FGFR1 as a therapeutic target in lung cancer

About 30-40% of non small cell lung cancer (NSCLC) are either of adeno or squamous cell in origin. Despite similar incidence, our understanding of therapeutically relevant molecular alterations that drive squamous cell carcinoma (SCC) tumorigenesis remains much less understood than adeno carcinoma (AC). Continued understanding of therapeutically relevant molecular alterations that drive the subtype specific tumorigenesis hence remain of vital significance to improve prognosis and treatment of the disease. Here, we describe high-level amplification of 8p11-12 chromosomal segment encompassing the FGFR1 locus in 44 of 732 (6%) of non-small cell lung carcinoma (NSCLC) samples which occurs most commonly in the squamous cell subtype of NSCLC (21%). We show that treatment of at least one NSCLC cell line harboring focally amplified FGFR1 with FGFR1-specific shRNAs or with the FGFR small molecule inhibitor PD173074 leads to cell growth inhibition. These studies show that FGFR1 activity preferentially promotes squamous lung cancer cell survival, and that inhibition of FGFR1 by targeted therapy might be a mechanism that could be exploited to customize subtype specific treatment. Given that targeted therapies for NSCLC are limited to the adenocarcinoma subtype at this time, this work provides a potential first therapeutic target for patients with squamous cell lung cancer.