Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer
Gynecologic Oncology Nov 04, 2020
Elayapillai S, Ramraj S, Benbrook DM, et al. - In this study, researchers performed a controlled evaluation of mebendazole's therapeutic efficacy in cell culture and in vivo models of ovarian cancer. As ovarian cancers, in majority, harbor p53 null or missense mutations, researchers here evaluated the effects of p53 mutations and a mutant p53 reactivator, PRIMA-1MET (APR246) on mebendazole activity. Evaluation of mebendazole was done in xenograft (PDX) models derived from cisplatin-resistant high grade serous stage 3C ovarian cancer patient: PDX-0003 (p53 null) and PDX-0030 (p53 positive), and on ovarian cancer cell lines: MES-OV (p53 R282W), ES2 (p53 S241F), A2780 (p53 wild type), SKOV3 parental (p53 null) and isogenic sublines, SKOV3 R273H p53 and SKOV3 R248W p53. Growth of ovarian cancer cell lines and high grade serous ovarian PDX tumors was inhibited by mebendazole. In an orthotopic ovarian cancer model of maintenance therapy, mebendazole led to inhibition of tumor establishment. Findings suggest that mebendazole's activity is correlated with p21 increase and tubule destabilization, and is complemented by mutant p53 reactivation. They support clinical development of mebendazole for ovarian cancer therapy and maintenance.
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