Small cell lung cancer (SCLC) is a fast-growing and highly aggressive type of lung cancer. Most patients are diagnosed at an advanced stage. Chemotherapy remains the standard first-line treatment, but many patients quickly develop resistance, leading to a very low five-year survival rate of around 7%. It is urgent to find new ways to improve treatment outcomes.

In a study published in Signal Transduction and Targeted Therapy, a research team led by Prof. LIU Qingsong from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences discovered a new drug candidate that may help overcome chemotherapy resistance in SCLC.

Researchers found that BMX and E2F1, proteins linked to cell growth and survival, are highly active in tumor samples and drug-resistant cancer cells. They 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.

Therefore, researchers developed a compound called IHMT-15137 which specifically blocks BMX activity, a key signaling pathway linked to drug resistance. IHMT-15137 disrupts the downstream signals and reduces E2F1 levels, making cancer cells more sensitive to the treatment.

Laboratory tests showed that when used together with the chemotherapy drug cisplatin, IHMT-15137 produced strong anti-tumor 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 Assoc. Prof. QI Shuang, one author of this study.

Small-molecule inhibitor targets BMX-E2F1 axis to reverse SCLC chemoresistance. (Image by QI Shuang)