Treatment of advanced squamous cell carcinoma of the lung: a review

Abstract

Lung cancer remains the single deadliest cancer both in the US and worldwide. The great majority of squamous cell carcinoma (SCC) is attributed to cigarette smoking, which fortunately is declining alongside cancer incidence. While we have been at a therapeutic plateau for advanced squamous cell lung cancer patients for several decades, recent observations suggest that we are on the verge of seeing incremental survival improvements for this relatively large group of patients. Current studies have confirmed an expanding role for immunotherapy [including programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition], a potential opportunity for VEGFR inhibition, and even future targets in fibroblast growth factor receptor (FGFR) and PI3K-AKT that collectively should improve survival as well as quality of life for those affected by squamous cell lung cancer over the next decade.

Keywords: Non-small cell lung carcinoma; angiogenesis inhibitors; epidermal growth factor receptor (EGFR); immunotherapy; squamous cell carcinoma of the lung.

Figure 1

Review of current and potential future therapies for squamous cell carcinoma (SCC) of the lung. EGFR, epidermal growth factor receptor; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; PD-1, programmed cell death-1; PD-L1, programmed cell death ligand 1; FGFR, fibroblast growth factor receptor; IGF, insulin-like growth factor.

Figure 2

Schematic of immune checkpoint mechanisms. Tumors can express PD-L1, which interacts with PD-1 on T-cells, leading to suppression of the antitumor T-cell response. PD-L1 and PD-1 inhibitors prevent this interaction, unleashing the T-cell antitumor response. Anti-CTLA-4 antibodies bind to CTLA-4 to increase the ratio of effector T-cells to negative regulatory T-cells to achieve the same effect. PD-1, programmed cell death-1; PD-L1, programmed cell death ligand 1; CTLA-4, cytotoxic T-lymphocyte-associated protein 4.