The Role of Mutations in -Mutated Non-Small-Cell Lung Cancer: Clinical Significance and Implications for Therapy.

Non-Small-Cell Lung Cancer (NSCLC) is the primary cause of cancer-related death worldwide. Oncogene-addicted patients usually benefit from targeted therapy, but primary and acquired resistance mechanisms inevitably occur. Tumor protein 53 () gene is the most frequently mutated gene in cancer, including NSCLC. mutations are able to induce carcinogenesis, tumor development and resistance to therapy, influencing patient prognosis and responsiveness to therapy. mutants present in different forms, suggesting that different gene alterations confer specific acquired protein functions. In recent years, many associations between different mutations and responses to Epidermal Growth Factor Receptor () targeted therapy in NSCLC patients have been found. In this review, we discuss the current landscape concerning the role of mutants to guide primary and acquired resistance to Tyrosine-Kinase Inhibitors (TKIs) -directed, investigating the possible mechanisms of mutants within the cellular compartments. We also discuss the role of the mutations in predicting the response to targeted therapy with EGFR-TKIs, as a possible biomarker to guide patient stratification for treatment.