Younger people with lung cancer may be more likely to have targetable genetic changes

A large international analysis of 14,246 people with non-small cell lung cancer (NSCLC) has found that younger adults were more likely than older adults to have genetic changes that can be matched with existing targeted treatments.

The findings come from a study led by researchers from Sylvester Comprehensive Cancer Center, Labcorp and Dana-Farber Cancer Institute and will be presented at the 2026 IASLC World Conference on Lung Cancer in Seoul on 14 September.

Nearly 58% of younger adults had guideline-recommended actionable alterations, compared with around 45% of people aged 55 and over.

What did the study find about younger people with lung cancer?

Researchers analysed genomic and immune data from 14,246 people with NSCLC.

They found that younger adults were more likely to have alterations in ALK, ROS1 and EGFR, all of which can help guide treatment decisions.

Older adults showed a different pattern. Their tumours were more likely to have KRAS-related changes and higher tumour mutational burden.

The researchers also found differences in immune markers, including LAG3 and TIGIT, which are being studied as possible targets for future immunotherapy strategies.

Importantly, the study does not suggest there is a simple cut-off where lung cancer suddenly becomes biologically different. The researchers describe a gradual shift in tumour biology with age.

Why could age be significant in lung cancer biology?

Lead author Dr Chinmay T. Jani, a medical oncologist at Sylvester Comprehensive Cancer Center, said the findings suggest age may be one part of the biological context researchers need to consider when interpreting biomarkers and developing more personalised treatment strategies.

He said:

“Our findings suggest that age may be an important piece of that puzzle.”

Senior author Dr Gilberto Lopes, Chief of Medical Oncology at Sylvester, said age should be considered alongside established biomarkers when evaluating treatment options.

The study suggests that the biology of NSCLC may change across the lifespan rather than being the same disease occurring at different ages.

Why are targetable genetic changes so important in lung cancer?

Some genetic alterations in NSCLC can be matched with targeted treatments.

Finding an alteration such as EGFR, ALK or ROS1 can therefore directly affect the treatment options available to someone with lung cancer.

This is why comprehensive biomarker testing is so important.

The new study does not mean that only younger people need biomarker testing, or that every younger adult will have a targetable alteration.

It does show that actionable alterations were particularly common in the younger group studied.

The researchers say the results support broader use of comprehensive genomic profiling, especially among younger adults with NSCLC.

Is lung cancer biologically different in younger adults?

There is growing evidence that lung cancer diagnosed at a younger age can have a different molecular profile.

This new analysis strengthens that evidence because of its size and because the researchers saw similar age-related patterns across multiple ancestry groups.

It also fits with a wider question researchers are trying to answer: why do some people develop lung cancer much earlier in life, including people with little or no smoking history?

We recently looked at the wider research into early-onset lung cancer, including possible biological, environmental and genetic explanations.

Read: The rise of early-onset lung cancer

What could this mean for lung cancer care?

For now, this study is mainly about understanding tumour biology and improving how genomic information is interpreted.

It could eventually help researchers:

• understand why certain alterations are more common at different ages

• refine biomarker interpretation

• improve treatment selection

• design future clinical trials

• identify groups that may need different approaches to screening or early detection

The researchers also note that younger adults generally fall outside current lung cancer screening criteria, making research into the biology and risk factors of early-onset lung cancer particularly important.

Younger adults and lung cancer: key points

• The analysis included 14,246 people with NSCLC.

• Nearly 58% of younger adults had guideline-recommended actionable alterations, compared with about 45% of people aged 55 and over.

• ALK, ROS1 and EGFR alterations were more common in younger adults.

• Older adults were more likely to have KRAS-related changes and higher tumour mutational burden.

• The researchers found a gradual shift in tumour biology with age rather than a clear divide between “young” and “old” lung cancer.

• The findings will be presented at the 2026 World Conference on Lung Cancer in Seoul.

Source: study announcement from Sylvester Comprehensive Cancer Center / Newswise, ahead of presentation at the 2026 IASLC World Conference on Lung Cancer.