New drug candidate shows promise in overcoming chemotherapy resistance in small cell lung cancer

A research team led by Prof. Liu Qingsong at the Institute of Health and Medical Technology, the Hefei Institutes of Physical Science of the Chinese Academy of Sciences has discovered a new drug candidate that may help overcome chemotherapy resistance in small cell lung cancer (SCLC). The study, published in Signal Transduction and Targeted Therapy, introduces a compound called IHMT-15137, which works by blocking a key signaling pathway linked to drug resistance.

SCLC is a fast-growing, highly aggressive type of lung cancer, accounting for about 15% of all cases. Most patients are diagnosed at an advanced stage. While chemotherapy remains the standard first-line treatment, many patients quickly develop resistance, leading to a very low five-year survival rate of around 7%. Finding new ways to improve treatment outcomes is therefore a major priority.

The researchers found that BMX and E2F1, proteins linked to cell growth and survival, are highly active in tumor samples and drug-resistant cancer cells. Further investigation showed that BMX helps stabilize E2F1, allowing cancer cells to continue growing, repairing damage and spreading, even under chemotherapy. This process plays a key role in making the cancer resistant to treatment.

Based on this finding, the team developed IHMT-15137, a molecule that specifically blocks BMX activity. By doing so, it disrupts the downstream signals and reduces E2F1 levels, making cancer cells more sensitive to treatment.

Laboratory tests showed that IHMT-15137, when used together with the chemotherapy drug cisplatin, produced strong antitumor effects in drug-resistant cancer cells, as well as in patient-derived tumor models. The combination treatment slowed tumor growth, triggered cancer cell death and showed minimal side effects in animal studies.

“Our findings suggest a new way to overcome chemotherapy resistance in small cell lung cancer by targeting key proteins early in the pathway,” said Associate Professor Qi Shuang.

Provided by
Hefei Institutes of Physical Science, Chinese Academy of Sciences

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