title: Squamous-cell carcinomas of the lung: emerging biology, controversies, and the promise of targeted therapy.
abstract: Squamous-cell carcinomas of the lung (SQCLCs) are defined by unique clinicopathological and molecular characteristics that have evolved substantially over time. Historically, these neoplasms were the most common subtype of non-small-cell lung cancers and were regarded as central tumours with high molecular complexity without targetable genetic abnormalities. Today, the incidence of SQCLCs is surpassed by adenocarcinomas of the lung with a shift towards peripheral squamous tumours. Differential responses to cytotoxic and biological treatments have reshaped our approach to standard therapies. Additionally, evidence of unique biology has emerged with the discovery of SOX2 amplification, NFE2L2 and KEAP1 mutations, PI3K pathway changes, FGFR1 amplification, and DDR2 mutations. These discoveries have ushered in a new era of targeted therapeutic agents for patients with this disease. This Review draws attention to the distinct clinical and pathological characteristics of SQCLCs, summarises present experience with existing cytotoxic and targeted therapies, and discusses emerging treatments based on new insights into the biology of this disease.
authors.affiliation: Department of Medicine Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drilon
authors.forename: Natasha
authors.initials: N
authors.lastname: Rekhtman
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Paul
authors.initials: P
authors.lastname: Paik
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D000070818:Discoidin Domain Receptors; D005784:Gene Amplification; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000072019:Kelch-Like ECH-Associated Protein 1; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D011975:Receptors, Mitogen / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C081876:CKAP4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; C117307:KRAS protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011975:Receptors, Mitogen; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins