Squamous Non-small Cell Lung Cancer as a Distinct Clinical Entity

Traditionally, the treatment of lung cancer has been based on histologic type [non-small cell lung cancer (NSCLC) or small cell lung cancer], performance status, and stage of disease. However, more recently, treatment decisions are being made based on molecular and histologic characteristics of the tumor. Specifically, the sub-classification of NSCLC as squamous or nonsquamous is important in the context of newer treatments because clinical data have demonstrated differences in the tolerability and activity of these agents. Although progress continues to be made in the treatment of nonsquamous NSCLC, a significant unmet need exists for patients with squamous NSCLC. For both targeted and chemotherapeutic agents, the majority of regulatory approvals and updates to clinical practice guidelines for advanced NSCLC have focused on nonsquamous disease. In addition, because of safety concerns, patients with squamous NSCLC have been excluded from a number of clinical trials of investigational agents, particularly those targeting angiogenesis. This review discusses the importance of histology for treatment selection in NSCLC and summarizes recently completed and ongoing trials of investigational agents in squamous NSCLC. In addition, exciting developments in next-generation sequencing of squamous NSCLC have highlighted differences between squamous and nonsquamous disease and revealed potential new therapeutic targets. Advances in the molecular genetics of squamous NSCLC and implications for therapy will also be reviewed. Although progress in squamous NSCLC has faced limitations, momentum is building toward the identification of more effective treatments for this patient population.