Squamous Cell Lung Cancer: Review of Biochemical Aspects, Cellular Signals, and Pharmacological Treatments

Document Type : Review Articles

Authors

National Guard Health Affairs, Jeddah, Saudi Arabia

Abstract

Background: Squamous cell carcinoma (SCC) of the lung is the second most common non-small cell lung cancer (NSCLC), strongly associated with smoking and central airway location. Despite declining incidence due to reduced smoking rates, it remains a major cause of cancer mortality, with unique histopathological and molecular features distinguishing it from other NSCLC subtypes.

Aim: This review examines the biochemical pathways, cellular signaling, diagnostic approaches, and evolving treatment paradigms for SCC, emphasizing recent advances in immunotherapy and targeted therapy.

Methods: A comprehensive analysis of peer-reviewed literature was conducted, focusing on SCC epidemiology, pathogenesis (particularly tobacco-induced carcinogenesis), diagnostic imaging/pathology criteria, and evidence-based treatment strategies across disease stages.

Results: SCC accounts for ~30% of NSCLCs, characterized by keratin pearls/intercellular bridges on histology. Diagnosis relies on CT/PET imaging and immunohistochemistry (p40/p63 positivity). Treatment is stage-dependent: surgery for early-stage (IA-IIB), chemoradiation for locally advanced (IIIA-IIIB), and platinum-based chemotherapy ± immunotherapy (pembrolizumab/cemiplimab) for metastatic disease. PD-L1 expression ≥50% predicts immunotherapy response. Unlike adenocarcinoma, targetable mutations (EGFR/ALK) are rare (<5%), though emerging agents show promise for FGFR1/PIK3CA alterations.

Conclusion: SCC management requires multidisciplinary integration of surgery, radiation, systemic therapy, and molecular profiling. Immunotherapy has improved survival in advanced disease, but limited targeted options underscore the need for biomarker discovery. Smoking cessation remains paramount for prevention.

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Egyptian Journal of Chemistry
Volume 68, Issue 13 - Serial Number 13
(In Loving Memory of Late Professor Doctor”Zeinab M. Nofal” In progress
December 2025
Pages 619-630

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History

  • Receive Date: 04 July 2025
  • Revise Date: 27 August 2025
  • Accept Date: 05 September 2025

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