KRAS Mutations in Squamous Cell Carcinomas of the Lung

Abstract

KRAS is one of the most commonly mutated oncogenes in cancer, enabling tumor proliferation and maintenance. After various approaches to target KRAS have failed over the past decades, the first specific inhibitor of the p.G12C mutation of KRAS was recently approved by the FDA after showing promising results in adenocarcinomas of the lung and other solid tumors. Lung cancer, the most common cancer worldwide, is a promising use case for these new therapies, as adenocarcinomas in particular frequently harbor KRAS mutations. However, in squamous cell carcinoma (SCC) of the lung, KRAS mutations are rare and their impact on clinical outcome is poorly understood. In this review, we discuss the current knowledge on the prevalence and prognostic and predictive significance of KRAS mutations in the context of SCC.

A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs

“…Current studies on NSCLC are more focused on the pathological subtypes of lung adenocarcinoma (LUAD), while less attention is paid to the pathological subtypes of lung squamous cell carcinoma (LUSC) ( Hirsch et al, 2017 ; Felip et al, 2021 ; Thai et al, 2021 ). According to traditional studies, the overall progress of LUSC is slow and the prognosis of patients is better ( Acker et al, 2021 ; Wang J. et al, 2021 ; Nicholson et al, 2022 ). However, severe LUSC can block the trachea and cause obstructive lung function damage.…”

Definitive Chemoradiation and Durvalumab Consolidation for Locally Advanced, Unresectable KRAS-mutated Non-Small Cell Lung Cancer

“…Yet, it has been acknowledged that certain clinically significant mutations, such as KRAS, STK11, KEAP1, and TP53, are found in squamous cell carcinomas. [40][41][42] In the era of precision oncology, comprehensive molecular profiling with next-generation sequencing for actionable genes as well as clinically meaningful non-actionable genes in stage III disease is needed to guide appropriate treatments. Considering financial and access limitations, comprehensive genomic profiling should be offered to all patients with stage III NSCLC not only to guide treatment decisions for consolidation with durvalumab, but also to advise the next lines of therapy and clinical trials and characterize how immunotherapy may select for resistance by comparing to post-progression sequencing.…”

Daily Practice Assessment of KRAS Status in NSCLC Patients: A New Challenge for the Thoracic Pathologist Is Right around the Corner

“…Depending on the population and the series, the frequency of KRAS mutations in lung cancer patients is variable, identified in around 20% to 40% of lung adenocarcinomas and in around 5% to 7% of lung squamous cell lung carcinomas [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. These mutations are much more frequent in Caucasian and Hispanic populations (from 25% to 35%) than in Asian populations (including Chinese and Indian patients) and in Iranians (globally from 9% to 13%) [ 59 , 61 , 62 , 63 , 65 , 66 , 67 , 68 ].…”