p53 Co-mutations in EGFR-mutant NSCLC: biological insight and therapeutic implications

Non-small cell lung cancer (NSCLC) harbouring mutations in the epidermal growth factor receptor (EGFR) represents a well-defined molecular subset that is amenable to targeted therapies. However, clinical heterogeneity in treatment response and resistance highlights the critical need for a deeper understanding of co-occurring genetic alterations. Among these, TP53 mutations are the most frequent co-mutations observed in EGFR-mutant NSCLC and are increasingly recognized for their prognostic and predictive relevance. With the emergence of next-generation sequencing in routine diagnostics and the growing arsenal of targeted therapies, the time is ripe to comprehensively assess how p53 co-mutations shape tumor biology, influence drug resistance, and impact patient outcomes. This review integrates recent mechanistic insights with therapeutic strategies and emerging clinical data, offering a timely and cohesive synthesis of a rapidly evolving field. The biological function of p53, its role in EGFR-mutant lung cancer, and the implications for current and future therapies are discussed.