Younger adults with non-small cell lung cancer are significantly more likely than older patients to have genetic alterations that can be matched with targeted therapies, according to a large international study led in part by researchers at Sylvester Comprehensive Cancer Center part of the University of Miami Miller School of Medicine. The findings will be presented Sept. 14, in Seoul, Republic of Korea, at the 2026 World Conference on Lung Cancer.
Analyzing genomic and immune data from 14,246 patients, researchers from Sylvester, Labcorp and Dana-Farber Cancer Institute found nearly 58% of younger patients had guideline-recommended actionable alterations, compared with about 45% of patients age 55 and older, suggesting age may be an important factor in understanding tumor biology and tailoring treatment.
Key findings:
- Younger adults were more likely to have molecular changes that can be matched with existing targeted therapies.
- Younger patients were more likely to have ALK, ROS1 and EGFR alterations, which can help guide treatment decisions.
These findings can help physicians better identify which patients may benefit from targeted therapies and support more personalized treatment plans.
Older patients showed a different pattern. Their tumors were more likely to have KRAS-related changes and a higher tumor mutational burden, meaning the cancer carried more mutations overall.
Researchers also found age-related differences in immune markers, including LAG3 and TIGIT, which are being studied as possible targets for future immunotherapy strategies.
The findings point to a gradual shift in tumor biology with age, not a hard divide between younger and older patients.
"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," said Chinmay T. Jani, M.D., medical oncologist at Sylvester and lead author of the study. "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."
"Age should be considered alongside traditional biomarkers when evaluating treatment options for patients with lung cancer," said Gilberto Lopes, M.D., Sylvester's chief of medical oncology, associate director and medical director for international affairs and senior author of the study. "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."
The study supports broader use of comprehensive genomic profiling, especially for younger adults diagnosed with non-small cell lung cancer. Testing can help doctors identify whether a tumor has a genetic driver that may respond to a targeted therapy.
The researchers also saw consistent age-related patterns across multiple ancestry groups, strengthening the evidence that age may influence the molecular drivers of lung cancer.
Younger adults generally fall outside current lung cancer screening eligibility criteria. Research like this can help identify high-risk populations and inform future efforts to expand or refine screening guidelines to support earlier detection.
Age may help explain why lung cancers behave differently from one patient to another. The findings could help researchers refine how doctors interpret biomarkers and choose more individualized treatment strategies.
Researchers say the results add to growing evidence that precision medicine should account not only for what mutations are present, but also for how tumor biology changes over a patient's lifetime.
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