SMURF2 Inhibitors Increase Effectiveness of MEK Inhibitors

Treatments that target a protein called MEK could work better when combined with drugs that inhibit a protein called SMURF2, according to research in the British Journal of the National Cancer Institute. MEK is involved in cell division and can be activated by BRAF and NRAS mutations. However, melanomas often resist MEK inhibitors. The researchers found that MEK inhibitors made melanoma cells grown in the laboratory produce too much of a protein called SMURF2. This in turn led to overproduction of another protein called MITF, which protects melanomas against MEK inhibitors. When treated with both a MEK inhibitor called selumetinib and a SMURF2 inhibitor, tumor growth was suppressed by 98% in mice.

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Treatment Breaks May Delay or Prevent Vemurafenib Resistance

Giving melanoma patients a break from vemurafenib could make this treatment more effective. Research in Nature shows that vemurafenib-resistant tumors keep growing during treatment because they produce high levels of mutated BRAF proteins, which are involved in cell division. Moreover, these tumors actually depend on the drug to grow. In contrast, an on-and-off treatment schedule can help keep melanomas from becoming resistant to vemurafenib in mice.

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New Clinical Trial to Determine if PV-10 Boosts Immune System

The experimental drug PV-10, which is injected directly into melanoma tumors, may work partly by boosting the immune system. To find out, researchers are launching a clinical trial to see if patients treated with PV-10 have immune biomarkers in their tumors and blood. The study will enroll up to 15 patients.

Testing Lymph Nodes Near Melanomas May Not Help

A British Medical Journal report questions an invasive, expensive standard practice for melanoma patients in the U.S. Called sentinel node biopsy, the approach involves testing lymph nodes near tumors for cancer cells and removing nodes that test positive. The report cites a 2006 study showing that sentinel node biopsy did not increase 5-year survival rates and calls for further analysis of the practice’s effectiveness. Sentinel node biopsies are not standard in the UK.

Researchers Write New Guide to Optimal Treatments for Melanomas with BRAF Mutations

Based on current data, researchers have developed a new treatment guide for melanomas with the most common mutations (BRAF V600). While these melanomas can be targeted with vemurafenib and dabrafenib, challenges remain. Not all tumors respond, some become resistant, and side effects can include another type of skin cancer called squamous cell carcinoma. Other treatment options include trametinib, which targets a protein called MEK, as well as immunotherapies such as high-dose interleukin 2 and ipilimumab, both of which can control tumors completely.

Melanoma Can Still Recur When Lymph Nodes Test Clear

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.

Melanoma Apps No Substitute for Doctors

A JAMA Dermatology study shows the dangers of using smartphone apps to self-diagnose melanomas. The researchers compared diagnoses of 60 melanomas and 128 benign lesions by a board-certified dermatopathologist to those of four apps. Three of the apps incorrectly said that 30% or more of the melanomas were harmless. The fourth app, which sent images to board-certified dermatologists, was better, but still misdiagnosed one of the melanomas as benign. These apps are not subject to regulatory oversight.

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Mutation Linked to Less Risk of Spreading in Eye Melanomas

A genetic abnormality may help predict which melanomas in the eye are unlikely to spread, according to a study in Nature Genetics. The researchers found that nearly 20% of 102 people with eye melanomas had a mutation in a gene called SF3B1. These people were usually younger when diagnosed and their tumors were less likely to spread and become deadly.

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Genentech Adds MEK Inhibitor to Phase III BRAF Inhibitor Trial

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.