HIV drug increases therapeutic window for skin cancer by slowing drug resistance

As our understanding of the way drugs target specific diseases grows, researchers have begun connecting more of the dots, spotlighting the ways in which drugs initially developed to target one ailment may hold promise in others.

Now researchers from Cancer Research UK have shown that an HIV drug may be effective in halting skin cancer by preventing its associated drug-resistance--increasing the therapeutic window to reverse cancer progression.

CRUK scientists based out of the University of Manchester publish their work this month in the journal Cancer Cell. They took a group of 11 patients who were on the standard treatment for melanoma--including patients on a single drug (vemurafenib) or a combination of drugs (dabrafenib and trametinib).

They observed after the initial exposure to the drug(s) the cancer used a molecular switch to briefly "rewire" itself to resist the anticancer effects of the drugs. After two weeks of treatment the researchers saw this became a permanent feature of the cancer and linked this resistance to genetic changes.

"In the first few weeks of standard treatment for skin cancer, the cancer cells become stronger and more robust against treatment," said Claudia Wellbrock, lead author of the study.

Using a known HIV drug (nelfinavir) they hypothesized it may be possible to delay drug resistance and make skin cancer drugs more effective, since the HIV drug works by blocking the same molecular switch required for cells to resist treatment. Using a mouse model to test this they showed the skin cancer treatment was indeed more potent when given with the HIV drug.

"If we can target skin cancer cells before they become fully resistant, we would have a much better chance of blocking their escape. And we think this research has brought us one step closer to making this a reality," said Wellbrock.

Nic Jones, director of CRUK's Manchester Cancer Research Center, added: "Melanoma can be difficult to treat because the cancer becomes resistant to drugs quite quickly. But this exciting research means we might be able to fight back by blocking the first steps toward resistance, so that treatments are effective for longer.

"While drug resistance is a big challenge, we're making great progress. Drug resistance in late stage skin cancer is still a big problem and something we need to tackle. We've seen big steps forward recently with the development of immunotherapies but this exciting approach could stop skin cancer developing resistance at an earlier point."

- here's the release
- here's the article abstract

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