Drug combo causes lung cancer cells to self-destruct

U.K. researchers have hit upon a drug combination that appears to combat lung cancer by triggering self-destruction in tumor cells.

Previously, scientists had pinpointed a protein called tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for its ability to induce apoptosis--self destruction--in cancer cells without causing toxicity in a living organism. But to date, TRAIL-receptor drugs have shown only limited therapeutic benefit in clinical trials because most primary human cancers are TRAIL-resistant.

To combat TRAIL resistance in cancer cells, investigators at Cancer Research UK went in search of a target that would allow TRAIL to destroy cancer cells--and they landed on CDK9.

In human lung cancer cells and a mouse model of lung cancer, researchers tested a combination of two drugs--TRAIL and a CDK9 inhibitor--and found that the drugs altered the molecular switches in the cell suicide process, causing the cancer cells to self-destruct. The CDK9 inhibitor--called SNS-032--in combination with TRAIL effectively induced apoptosis even in highly TRAIL-resistant cancer cells. Healthy cells eventually self destruct when they are no longer useful, but cancer cells are immortal and can divide and grow infinitely, forming tumors.

"Igniting the fuse that causes lung cancer cells to self-destruct could pave the way to a completely new treatment approach--and leave healthy cells unharmed" said Henning Walczak, a scientist at Cancer Research UK.

The findings will be presented at the upcoming National Cancer Research Institute (NCRI) Cancer Conference in Liverpool.

- get the study abstract
- read more from Cancer Research UK

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