Researchers turn cancer cells dormant with toxic drug analogs

OSU's Arup Indra

What if, instead of killing cancer cells, you could make them dormant? Making analogs of a highly toxic cell killer, pactamycin, investigators at Oregon State University say they have done just that. And while they're still working on a targeted delivery vehicle needed to make it safe, they add that this new approach has the potential for becoming a new class of cancer therapy that would be far "gentler" than the chemotherapies used today.

Pactamycin is known for killing cells indiscriminately by inhibiting protein synthesis, a toxicity problem that prevented its use. The researchers, though, made two analogs of pactamycin--TM-025 and TM-026--and used them to accelerate cell senescence in head and neck cancer cell lines. The same approach, they add, could likely work just as well in a number of different cancer types.

By turning a tumor vegetative, says the team, a targeted therapy may be more likely to avoid the kind of drug resistance that are spurred by many oncology therapies.

"A traditional view of chemotherapy is that you try to completely kill cancer cells and destroy tumors," said Arup Indra, an associate professor in the OSU College of Pharmacy and one of the lead authors on the study. "Sometimes this is effective, sometimes not as much. An alternative approach is to cause rapid cell aging and induce premature senescence, which we believe could become a new frontier in cancer drug development."

"With further research we hope to create a nontoxic nanocarrier that could provide targeted delivery of the TM-025 and TM-026 analogs specifically to cancer cells," said Gitali Indra, an OSU assistant professor and also a lead and corresponding author on the study. "In some cases, such as oral cancer, it may also be possible to use topical treatments. But this approach should have significant promise if we can develop techniques to adequately target the cancer cells.

- here's the release

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