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[4 min read] Compounds found that starve melanoma cells of energy
Researchers have identified compounds that starve melanoma cells of energy. Scientists at Oregon State University and Oregon Health & Science University have found a possible way of beating the drug resistance of melanoma, one of the deadliest forms of skin cancer.
The findings – published in Molecular Carcinogenesis – are significant because Australia is the skin cancer capital of the world, with around 2,000 deaths caused by melanoma every year. It kills by spreading to other organs such as the brain and lungs.
The research team in Oregon looked for ways to combat the drug resistance that metastatic melanoma cells often develop.
There have been breakthroughs in our understanding of the molecular basis for melanoma which have led to the development of drugs like vemurafenib and dabrafenib, which provide a dramatic clinical response in patients with metastatic melanoma. However, the effectiveness of these drugs is limited by a high resistance rate, which can lead to disease relapse within months.
The current five-year survival rate of stage 4 metastatic melanoma is less than 50 per cent.
Cancer cells have a metabolism (a chemical process that cells rely upon to thrive) that has been altered from that of normal cells. It was this metabolism that scientists directed their efforts towards in this research.
They tested almost 9,000 compounds against a vemurafenib-resistant melanoma cell line to see if any of them would halt proliferation or induce cell death.
They found that two structurally similar compounds interfered with the cancer cells’ metabolism. These were deguelin and rotenone: naturally occurring pesticides produced by many plant species. Further testing with deguelin showed that it inhibited oxygen consumption in the cells’ mitochondria, effectively starving the cells of energy.
Deguelin has been known as a treatment for other cancer types, but its use as a metabolic regulator in drug-resistant metastatic melanoma has not been shown before.
Further research in this field could lead to attractive treatment options for physicians managing patients with drug-resistant metastatic melanoma.
Source: Mitochondrial complex I inhibitor deguelin induces metabolic reprogramming and sensitizes vemurafenib‐resistant BRAFV600E mutation bearing metastatic melanoma cells. Molecular Carcinogenesis. 2019; 1‐ 11. https://doi.org/10.1002/mc.23068, , , et al.
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