MedicalResearch.com Interview with:
Bin Zheng, PhD
Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School
Charlestown, MA 02129
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Melanoma is the most deadly form of skin cancer with more than 75,000 newly diagnosed cases in the US each year. Over the years, various genetic driver mutations have been identified that cause melanoma, including mutations in the genes BRAF and NRAS. Recent genetic insights into the development of melanoma showed that also mutations in NF1 can lead to melanoma. While there are targeted therapies available for BRAF-mutant melanoma, thus far no such therapies are available for NF1-mutant melanoma. We identified that using a combination of an ERK inhibitor, SCH772984, and the antidiabetic drug phenformin could provide a novel therapeutic strategy for NF1-mutatnt melanomas.
MedicalResearch.com: What should readers take away from your report?
Response: Phenformin is very suitable combination partner for ERK inhibitors in NF1-mutant melanoma and more broadly for targeted therapies in melanoma, as we could previously show that synergy also exists in combination with BRAF inhibitors in BRAF-mutant melanoma. Phenformin was withdrawn from the market in the 1970-ies due to side-effects that were deemed too severe for diabetic patients. However, compared to most anticancer drugs, the side-effect profile of phenformin is actually very favorable and there are extensive efforts going on – including here at Massachusetts General Hospital and the Memorial Sloan Kettering Cancer Center in New York – to repurpose phenformin for its use in cancer. A phase I clinical trial of phenformin in combination with dabrafenib and trametinib for patients with BRAF-mutated melanoma is currently ongoing (https://clinicaltrials.gov/ct2/show/NCT03026517). Our study underlines the importance of these efforts and sheds further light on the multifaceted anticancer activities of phenformin.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The development of ERK inhibitors has been challenging due to toxicity issues. Future studies using alternative ERK inhibitors that are currently going through various stages of clinical trials are needed to validate these results. Furthermore, the results from the currently ongoing trial of phenformin in BRAF-mutant melanoma are needed to bring phenformin back on the market. Once this happens, our results can be quickly implemented into clinical trials in NF1-mutant melanoma.
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Phenformin enhances the efficacy of ERK inhibition in NF1-mutant melanoma.
Trousil S1, Chen S2, Mu C3, Shaw FM4, Yao Z5, Ran Y6, Shakuntala T5, Merghoub T5, Manstein D1, Rosen N5, Cantley LC7, Zippin JH4, Zheng B8.
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