The Role of TP53 Mutations in EGFR -Mutated Non-Small-Cell Lung Cancer: Clinical Significance and Implications for Therapy.
Matteo CanaleKalliopi AndrikouIlaria PrianoPaola CraveroLuigi PasiniMilena UrbiniAngelo DelmonteLucio CrinòGiuseppe BrontePaola UliviPublished in: Cancers (2022)
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 ( TP53 ) gene is the most frequently mutated gene in cancer, including NSCLC. TP53 mutations are able to induce carcinogenesis, tumor development and resistance to therapy, influencing patient prognosis and responsiveness to therapy. TP53 mutants present in different forms, suggesting that different gene alterations confer specific acquired protein functions. In recent years, many associations between different TP53 mutations and responses to Epidermal Growth Factor Receptor ( EGFR ) targeted therapy in NSCLC patients have been found. In this review, we discuss the current landscape concerning the role of TP53 mutants to guide primary and acquired resistance to Tyrosine-Kinase Inhibitors (TKIs) EGFR -directed, investigating the possible mechanisms of TP53 mutants within the cellular compartments. We also discuss the role of the TP53 mutations in predicting the response to targeted therapy with EGFR-TKIs, as a possible biomarker to guide patient stratification for treatment.
Keyphrases
- epidermal growth factor receptor
- small cell lung cancer
- advanced non small cell lung cancer
- tyrosine kinase
- end stage renal disease
- ejection fraction
- newly diagnosed
- chronic kidney disease
- prognostic factors
- genome wide
- stem cells
- squamous cell carcinoma
- gene expression
- brain metastases
- small molecule
- binding protein
- combination therapy
- squamous cell
- replacement therapy
- lymph node metastasis