Scientists discover new hope for never-smoker lung cancer

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While smoking is the leading cause of lung cancer, there is a growing number of lung cancer cases among people who have never smoked, particularly women.

These patients often face limited treatment options, with many receiving chemotherapy that has severe side effects and low effectiveness.

This highlights the urgent need for new targeted therapies.

A team of researchers, led by Dr. Lee Cheolju at the Korea Institute of Science and Technology (KIST), Dr. Kim Seon-Young at the Korea Research Institute of Bioscience and Biotechnology, and Dr. Han Ji-Youn at the National Cancer Center, has discovered new pathways for treating never-smoker lung cancer.

Their findings, published in the journal Cancer Research, reveal that estrogen signaling pathways are overexpressed in certain Korean patients with never-smoker lung cancer.

Using advanced multi-omics analysis, which combines various types of molecular data, the research team studied tissue samples from 101 Korean never-smoking lung cancer patients. These samples were part of a larger group of 1,597 patients who visited the National Cancer Center over the past decade.

The researchers distributed clinical information and data from genomic, transcriptomic, proteomic, and phosphoproteomic analyses to understand the disease better.

The proteomic analysis, which measures proteins in the samples, was particularly challenging. The team used isotopic labeling techniques to analyze an average of over 9,000 proteins and 5,000 phosphorylated proteins per sample with only 100 micrograms of protein, a tenth of the usual amount needed.

Their analysis identified mutations in genes like STK11 and ERBB2, which are known to be associated with cancer. They also found that estrogen signaling pathways were overexpressed, even though there were no significant changes in estrogen hormone receptors.

Based on these findings, the researchers tested the anti-cancer drug saracatinib, which inhibits a protein involved in estrogen signaling. They found that saracatinib significantly increased cell death in cancer cells with mutations in STK11 and ERBB2 compared to those without such mutations.

The research team is now developing a molecular diagnostic technique to identify patients with overexpressed estrogen signaling pathways. They also plan to conduct preclinical trials to test the effectiveness of saracatinib on never-smoking lung cancer in animal models in collaboration with the National Cancer Center.

Dr. Lee Cheolju of KIST stated, “This successful discovery of new therapeutic targets for difficult-to-treat cancer through multi-omics analysis is a significant achievement of domestic research and collaboration between hospitals and research institutions. We aim to expand multi-omics research on human diseases based on this experience.”

This breakthrough offers new hope for never-smoker lung cancer patients, potentially leading to more effective and targeted treatments in the future.

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