A new drug combination could treat melanomas that resist therapy with a single drug, suggests research that appeared in Cancer Discovery on melanoma cells grown in the laboratory. The researchers tested melanoma cells that had BRAF mutations and resisted treatment with the BRAF inhibitor vemurafenib, and that had NRAS mutations, which resist many treatments. The most effective combination treatment was statins, which are commonly used to treat high cholesterol, but can also kill melanoma cells, and drugs that inhibit proteins called cyclin-dependent kinases, which are involved in cell division.
A JAMA Surgery study clarified when melanoma is likely to return in people determined to be cancer-free by sentinel lymph node biopsy. The researchers found that melanoma recurred in 16% of 515 such patients and that 4% of them had tumors in the lymph nodes that had been tested. Recurrence was more likely when the initial tumors were on the head or neck and were deeper (2.7 vs. 1.8 mm). Recurrence was less likely in women and in people who were younger when first diagnosed.
Pharmaceutical firm GlaxoSmithKline has started a phase III study to see if a drug combination can prevent or delay the recurrence of melanomas with BRAF V600 mutations. Both drugs—dabrafenib, a BRAF inhibitor and trametinib, a MEK inhibitor—are experimental; the study will assess the efficacy and safety of the combination. The researchers plan to enroll about 850 people from more than 200 sites worldwide in the study. Another pharmaceutical firm, Roche, is also doing late-stage trials of a different BRAF inhibitor/MEK inhibitor combination.
Biotech company Genentech has added a MEK inhibitor to a phase III trial of vemurafenib, an FDA-approved BRAF inhibitor. MEK inhibitors have been shown to counteract resistance to BRAF inhibitors. The experimental MEK inhibitor is called GDC-0973, and is also known as XL-518 or RG7421. Vemurafenib (Zelboraf®) targets melanomas with BRAF V600 mutations, which are found in about half of these aggressive skin cancers. Genentech is part of the Roche Group; the two companies are conducting this combination treatment trial jointly.
New research in Nature shows that the immune system can control tumors permanently without destroying cells. The researchers treated cancers with two proteins that activate the immune system (interferon-g and tumor necrosis factor) and found that the combination kept tumors from growing by making the cells dormant. This work could ultimately lead to cancer treatments that are both effective and free of side effects, suggesting that we shift from the “war on cancer” strategy of killing tumor cells to focus instead on restoring the body’s innate ability to arrest tumor development.