Age-Related Genomic Differences Could Refine Treatment Decisions in Lung Cancer

Non-small cell lung cancer (NSCLC) has highly heterogeneous molecular profiles that influence therapy selection, including eligibility for targeted treatments. As clinicians increasingly rely on comprehensive genomic profiling to identify actionable alterations, understanding how tumor biology varies with age may help refine treatment decisions. To clarify these age-related differences, investigators compared genomic and immune features across patient groups, finding that younger adults harbor more targetable alterations while older adults exhibit distinct molecular and immune characteristics that may also influence care.

The University of Miami Miller School of Medicine’s Sylvester Comprehensive Cancer Center, together with Labcorp and Dana-Farber Cancer Institute, analyzed genomic and immune data from 14,246 people with NSCLC. The large, international effort compared age groups and assessed the prevalence of guideline-recommended actionable alterations alongside immune markers. The analysis will be presented at the 2026 World Conference on Lung Cancer, scheduled for September 12–15.

Younger adults were more likely to harbor molecular changes that can be matched with existing targeted therapies, with nearly 58% carrying guideline-recommended actionable alterations compared with about 45% of patients aged 55 and older. Alterations in ALK, ROS1, and EGFR were enriched in younger patients, while older patients more often exhibited KRAS-related changes and higher tumor mutational burden. Researchers also observed age-related differences in immune markers, including LAG3 and TIGIT, indicating immunologic divergence alongside genomic trends.

The investigators reported that these patterns were consistent across multiple ancestry groups and reflected a gradual biological shift with age rather than a sharp divide. The work supports broader use of comprehensive genomic profiling, particularly in younger adults with NSCLC, to clarify whether a tumor contains a driver alteration that can inform therapy selection. The study also notes that younger adults generally fall outside current lung cancer screening eligibility criteria, and that identifying high-risk populations could inform future efforts to refine screening approaches.

“As precision medicine continues to evolve, we need to think beyond identifying individual mutations and begin understanding the broader biologic context in which those mutations occur. Our findings suggest that age may be an important piece of that puzzle. By better understanding how tumors change across the lifespan, we can continue refining how we interpret biomarkers, develop new therapies and personalize treatment strategies for patients with lung cancer,” said Chinmay Jani, M.D., medical oncologist at Sylvester and lead author of the study.

“Age should be considered alongside traditional biomarkers when evaluating treatment options for patients with lung cancer. As we learn more about the factors that influence how individual tumors behave, we can make more informed treatment decisions and continue advancing truly personalized cancer care,” said Gilberto Lopes, M.D., Sylvester’s chief and professor of medical oncology, associate director and medical director for international affairs and senior author of the study.

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