Advances in molecular and immunologic targeted therapies for squamous cell carcinoma of the lung

While targeted therapy has revolutionized the treatment of some forms of non-small cell lung cancer (NSCLC) particularly adenocarcinoma of the lung, the standard treatments for advanced stage squamous cell carcinoma (SqCC) has remained platinum-doublet chemotherapy, and the prognosis remains poor. There remains a great need for breakthroughs in treatments for this common and deadly disease. Recently, a new understanding of the molecular and genetic makeup of SqCC, thanks to largescale genetic and molecular assays, has resulted in a number of targeted therapies entering clinical investigation for use in SqCC. Treatments targeting common mutations in SqCC have been studied in patient populations not preselected for mutations or overexpression and have had some early success. For example, the vascular endothelial growth factor receptor (VEFGR) inhibitor ramucirumab has been approved by the United States Food and Drug Administration (FDA) for use in certain settings for patients not selected for genetic mutations with NSCLC, including SqCC. Other agents are being investigated in selected populations with demonstrated genetic mutations or amplifications in the targeted pathway based on preclinical and early clinical data suggesting enhanced benefit in those groups. Early results in targeted immunotherapy have been particularly successful in SqCC compared to other histologic subtypes of NSCLC, and the programmed cell death 1 (PD-1) immune checkpoint inhibitor nivolumab has now been approved for second-line therapy in SqCC by the FDA. In this review, several oncogenic signaling pathways will be examined. The recent preclinical and clinical literature establishing those pathways as potential treatment targets, as well as ongoing clinical studies focused on those pathways, will be discussed. Recent and ongoing studies in targeted immune checkpoint inhibition and vaccine immunotherapy will also be reviewed.