Abstract 2501: Combination therapy with mebendazole, trametinib and metformin eliminates recalcitrant NRASQ61K melanoma cells

Autor: Maryam AbdusSamad, Cynthia M. Simbulan-Rosenthal, Anirudh Gaur, Dean S. Rosenthal, Edward C. McCarron
Rok vydání: 2016
Předmět:
Zdroj: Cancer Research. 76:2501-2501
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2016-2501
Popis: Melanoma is an aggressive and lethal form of cancer with increasing incidence worldwide. In recent years, the FDA approved several promising treatments for malignant melanoma. However, treatment often fails due to the survival and regrowth of drug-resistant cells. Studies by our lab and others suggest that Melanoma Initiating Cells (MIC), a CD133+ population that forms xenograft tumors, may represent an intermediate stage in the acquisition of stable drug resistance. This study aims to determine the effect of CD133-expression and drug resistance in metastatic melanoma cells harboring difficult-to-treat mutation signatures by focusing on the two main downstream cascades of MAPK and PI3K/AKT/mTOR. Our results show that triple combination therapy using mebendazole (repurposed anthelmintic BRAF inhibitor), trametinib (MEK inhibitor) and metformin (repurposed anti-diabetic mTOR inhibitor) synergistically reduces cell viability of NRASQ61K melanoma cells when compared with mebendazole, trametinib or metformin alone. Further, the surviving fraction from each monotherapy is highly enriched for CD133+ cells. Thus, the multi-kinase inhibitor trametinib, along with repurposed anthelmintic and anti-diabetic drugs may inhibit MAPK and PI3K/AKT/mTOR pathways, which could potentially be an effective therapy for the resistant subpopulation of melanoma initiating cells. Citation Format: Maryam AbdusSamad, Anirudh Gaur, Cynthia M. Simbulan-Rosenthal, Edward C. McCarron, Dean S. Rosenthal. Combination therapy with mebendazole, trametinib and metformin eliminates recalcitrant NRASQ61K melanoma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2501.
Databáze: OpenAIRE
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