Squamous Cell Carcinoma of the Lung: Molecular Subtypes and Therapeutic Opportunities

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Next to adenocarcinoma, squamous cell carcinoma (SCC) of the lung is the most frequent histologic subtype in non-small cell lung cancer. Encouraging new treatments (i.e., bevacizumab, EGFR tyrosine kinase inhibitors, and ALK inhibitors) have afforded benefits to patients with adenocarcinoma, but unfortunately the same is not true for SCC. However, many genomic abnormalities are present in SCC, and there is growing evidence of their biologic significance. Thus, in the short term, the molecular characterization of patients with SCC in modern profiling platforms will probably be as important as deciphering the molecular genetics of adenocarcinoma. Patients with SCC of the lung harboring specific molecular defects that are actionable (e.g., fibroblast growth factor receptor 1 amplification, discoidin domain receptor 2 mutation, and phosphoinositide 3-kinase amplification) should be enrolled in prospective clinical trials targeting such molecular defects.

Lung Squamous Cell Carcinomas with Basaloid Histology Represent a Specific Molecular Entity

“…All SCCs, either basaloid or not, showed very similar CNA profiles, pointing at regions previously reported (7), such as gain or amplicon of the 3q region around SOX2, found in almost all SCC samples. However, CNA are potentially highly informative concerning targeted therapies (24). In particular, FGFR1 (8p12) and MYB (6q22-q23), found here in peak regions of gain, are targetable: MYB could be targeted by several drugs under development (25,26), and FGFR1 amplified NSCLCs have been shown to be sensitive to FGFR1 inhibitors (27)(28).…”

Preclinical Antitumor Efficacy of BAY 1129980—a Novel Auristatin-Based Anti-C4.4A (LYPD3) Antibody–Drug Conjugate for the Treatment of Non–Small Cell Lung Cancer

“…Lung cancer is the most frequently diagnosed cancer with an estimated 1.8 million new cases in 2012 (9). NSCLC accounts for 85% of all lung cancers and SCC, being the second most frequent histologic subtype occurring in 30% of NSCLC cases, explains approximately 400,000 deaths per year worldwide (10).…”

FGFR1/3 Tyrosine Kinase Fusions Define a Unique Molecular Subtype of Non–Small Cell Lung Cancer

“…The activation of these kinases by amplification, mutations, or translocation plays crucial roles in cancer initiation and development (10,11). Recently, the FGFR gene rearrangements, including FGFR1, FGFR2, and FGFR3, were identified in diverse cancers, including glioblastoma, bladder cancer, cholangiocarcinoma, thyroid cancer, oral cancer, breast cancer, head and neck cancer, and lung SCC (12)(13)(14)(15).…”