Key Points
• Source: Molecular Biomedicine
• Relevance: “We briefly review the currently available techniques for KRAS mutation detection on biopsy and cytology samples. Finally, we discuss the new therapeutic strategies for targeting KRAS-mutant non-small cell lung cancer (NSCLC). These may herald a new era in the treatment of KRASG12Cmutated NSCLC as well as be helpful to develop demographic subsets to predict targeted therapies and prognosis of lung cancer patients.”
• In lung adenocarcinomas, mutations are present in 18 genes. KRAS mutations represent 33% of the total, with mutations present in exon 2 and exon 3, as well as codons 12, 13, and 61.
• With lung cancer, KRAS mutations usually involve codon 12 and 13, with codons 10, 61 and 146 rarely involved. The prevalence of KRAS mutations is similar in both early and advanced stage lung adenocarcinomas. A mixed continuum of KRAS mutations including transversions (80%) or transitions (20%) is noted in lung cancer patients. Transversions more usually predict adenocarcinoma vs transitions, which predict squamous cell carcinoma. Such mutations most often occur in men (60%), as well as current/former smokers with adenocarcinoma. The presence of KRAS mutations in small-cell lung cancer is rare.
• Up to one-third of KRAS-mutant lung cancers exhibit molecular heterogeneity. These differences predict chemotherapy response, tissue spread, and prognosis. Two active mutations result in either functional redundancy or cell senescence/death. Smokers with lung adenocarcinomas exhibit concurrent KRAS, TP53, STK11, or KEAP1 mutations vs non-smokers who have EGFR, TP53 mutations or MET alterations.