Cancer study identifies risks, new strategies for lung adenocarcinoma

Taipei, Aug. 22 (CNA) Taiwanese researchers have identified key traits of patients prone to recurrent lung adenocarcinoma and possible new strategies to detect and treat it, as part of an Academia Sinica-led project in collaboration with the U.S. Cancer Moonshot initiative.

The study by Chen Yu-ju (陳玉如), a distinguished research fellow at Academia Sinica's Institute of Chemistry, found that certain patients had high fatality rates despite being diagnosed with early-stage cancers.

It also found that people from different parts of the world as well as men and women were vulnerable to a range of intrinsic and external factors in different ways.

Chen's team drew on data and samples of 406 lung adenocarcinoma patients across eight countries in Asia, Europe and North America, and classified those patients into three groups based on proteomics -- the large-scale study of proteins.

One group labeled as "C2" was found to have a high risk of recurrence and metastasis, showing proteomic features similar to advanced tumors despite being clinically diagnosed at Stage I, Chen said.

"It was striking that among those [C2] stage I patients, only about half survived after five years," she said.

"This shows that although they were clinically diagnosed at an early stage, their proteomic profiles overlapped with those of late-stage patients -- in other words, they were very likely to relapse and die early," Chen said.

To help identify those "C2" patients, Chen's team designed a prototype blood test to detect such high-risk, "late-like" subtype of patients.

The test, targeting four protein biomarkers, has achieved an 85 percent sensitivity rate, though further clinical validation is still needed, she said.

Chen said her team's results were significant in two ways. First, being able to identify high-risk, early-recurrent patients will allow more timely active treatment or closer follow-up.

Also, she said, the results provide a blueprint for developing combination therapy or novel drug target for these late-like patients.

The study is significant given that lung cancer remained Taiwan's deadliest type of cancer in 2024, claiming 10,495 lives, according to Ministry of Health and Welfare data.

Factors in lung cancer

Chen said the team's research also looked into the roles of both intrinsic and external factors in lung adenocarcinoma.

Intrinsic factors cover genetic differences and protein expression while external ones include diet and environmental carcinogens.

"While external factors are important...not everyone exposed to them develops cancer," Chen said.

Her team found in cell experiments that Westerners were more susceptible than East Asians to relatively high concentrations of air pollutants such as benzo[a]pyrene -- a type of PAH (polycyclic aromatic hydrocarbons) -- which led to greater invasiveness and growth of specific types of cancer cells.

When pollutant concentrations were relatively lower, the results in Westerners and East Asians were reversed, which Chen described as "very interesting."

"This may also suggest that East Asian patients could already be affected by low concentrations of air pollution," the scholar said, noting that regardless of the type of carcinogen, air pollution overall promotes cancer progression across ethnic backgrounds.

The team also highlighted differences in lung adenocarcinoma progression between men and women, finding that male patients were more often affected by external carcinogens, while female patients were more likely influenced by intrinsic factors.

Such insights indicated that treatment strategies should be tailored to both gender and carcinogen-exposure pathways, Chen said.

To achieve that goal, Chen said her team pinpointed multiple protein sites that are highly expressed in specific subtypes and essential for cancer cell survival.

By identifying those sites, researchers can explore the repurposing of existing U.S. FDA-approved drugs, while also highlighting new targets for future drug development, according to Chen.

The latest findings from Chen's team were published in July in the international medical journal Cancer Cell, in a research article titled "Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures," co-authored with other scholars in the U.S. Cancer Moonshot initiative.

Chen and her team have been part of the Academia Sinica-led Taiwan Cancer Moonshot Project, launched in 2016 in collaboration with the U.S. Cancer Moonshot initiative led by then-U.S. Vice President Joe Biden.