Tumor Mutation Marker Helps Refine Lung Cancer Prognosis and Guide Therapy Selection

Lung cancer remains the leading cause of cancer death worldwide, while heterogeneous tumor genetics continue to complicate treatment decisions. Although molecular testing is increasingly used to match patients with targeted therapies, reliable prognostic markers remain limited in routine care, and data from underrepresented populations are scarce. A new study of Brazilian lung tumors shows that TP53 mutations correlate with prognosis and may help guide selection between targeted agents and chemotherapy.

A real‑world observational study conducted at Hospital de Amor de Barretos (Barretos, Brazil), with support from FAPESP (São Paulo, Brazil), comprehensively analyzed the genetic profile of lung tumors by evaluating 20 cancer‑associated genes in samples from 1,131 patients treated at its centers in Barretos and Porto Velho. The cohort included individuals from all five Brazilian macroregions, with notable representation from the Western Amazon. The analysis documented regional and ancestry‑related variation and found clinically relevant alterations in 88% of cases.

Alterations most frequently involved TP53 (58%), KRAS (25.6%), EGFR (20.6%), and ALK (6.6%). TP53 variants were more prevalent in individuals with greater African ancestry. Crucially, TP53 mutations were associated with worse prognosis, particularly among patients who also had EGFR mutations, a group that generally benefits from targeted therapies.

Investigators note that TP53, historically absent from routine reports and clinical decision‑making, is now being incorporated into the institution’s workflow to inform therapy choice. The findings indicate that concurrent EGFR and TP53 mutations are linked to reduced benefit from EGFR‑targeted therapy, while tumors with TP53 mutations may respond better to chemotherapy. The results were published in The Lancet Regional Health—Americas.

Despite advances, access to broad genetic testing is limited in Brazil’s public health system, the Sistema Único de Saúde (SUS), although standalone funding for EGFR gene testing was recently approved by the National Commission for the Incorporation of Technologies in the SUS (CONITEC). The study authors suggest these data can guide policy on which tests and therapies to prioritize, and they report that 12% of tumors had no known genetic alterations. Planned next steps include whole‑genome analyses and exploration of approaches to reactivate TP53 function.

"Even when receiving the most modern treatment, patients with TP53 mutations fared worse", said Rui Manuel Reis, scientific director of the Hospital de Amor Institute of Teaching and Research and one of the coordinators of the study.

"We've now incorporated it into our routine because we've discovered that this information can help guide the best therapeutic choice. In other words, patients with mutations in both EGFR and TP53 respond less well to EGFR-targeted therapy and may be ideal candidates for new clinical trials," said Rui Manuel Reis, scientific director of the Hospital de Amor Institute of Teaching and Research.

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