Medication used to treat human immunodeficiency virus can also help skin cancer patients. New research reveals that the HIV drug called nelfinavir stops skin cancer cells from developing drug resistance to targeted therapies.
Researchers in the latest study looked at the tumors of 11 patients with melanoma skin cancers. All participants in the study were on standard cancer treatments with vemurafenib or a dabrafenib and trametinib combination.
Researchers examined nelfinavir-affected skin cancer cells in mice and found that the HIV drug blocked the molecular switch that promoted cells' ability to survive and become resistant to treatment.
"We show that inhibiting MITF expression by nelfinavir has a potent enhancer effect on the action of BRAF and MEK inhibitors. Moreover, even in cells that do not display elevated expression of MITF, its relevance for melanoma cell survival appears to be sufficient for inhibitor sensitization," researchers wrote in the study.
"Our data suggest that apart from increasing initial responses also in NRAS mutant patients, the nelfinavir/MEK inhibitor combination could restore the MAPK inhibitor response in patients relapsed with increased NRAS signaling. Thus, by targeting a cancer-type-specific master regulator that plays an important role in the initial phases of drug-induced tolerance, we identify a clinical relevant approach for melanoma therapy," they added.
Lead researcher Claudia Wellbrock and her team at the University of Manchester said that the latest findings suggest that a combination of nelfinavir and currently approved skin cancer treatments can significantly improve drug potency by preventing tumors from developing drug resistance.
"In the first few weeks of standard treatment for skin cancer, the cancer cells become stronger and more robust against treatment," Wellbrock said in a news release.
"But 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," she explained.
"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 towards resistance, so that treatments are effective for longer," said professor Nic Jones, director of cancer research at the UK's Manchester Cancer Research Center.
"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," Jones added.
The findings are published in the journal Cancer Cell.
