FGFR as potential target in the treatment of squamous non small cell lung cancer

• Squamous lung cancers have been regarded as tumors without targetable molecular alterations.
• FGF/FGFR pathway deregulation is increasingly recognized across different tumors.
• FGF/FGFR pathway is one of the most promising druggable target in squamous lung cancers.
• FGFR amplifications, mutations, translocations are the most frequent mechanisms of activation.
• mAbs, ligand traps, TKIs directed versus FGF/FGFR are in development in lung tumor.

To date therapeutic options for squamous cell lung cancer patients remain scarce because no druggable targets have been identified so far. Aberrant signaling by FGFs (fibroblast growth factors) and FGFRs (fibroblast growth factors receptors) has been implicated in several human cancers and, particularly, in squamous non-small cell lung cancer (NSCLC).FGFR gene amplifications, somatic missense mutations, chromosomal translocations are the most frequent mechanisms able to induce aberrant activation of this pathway. Data from literature have established that the presence of an aberrant FGFR signaling has to be considered a possible negative prognostic factor but predictive of potential sensitivity to FGFR inhibitors.In the last years, clinical research efforts allowed to identify and evaluate promising FGFR inhibitors, such as monoclonal antibodies, ligand traps, non-selective or selective tyrosine kinase inhibitors. This review summarizes the current knowledge about FGFR alterations in NSCLC and the relative inhibitors in development, in particular in squamous NSCLC.