Oncotarget: Mebendazole Used to Treat Pancreatic Cancer
Channel: Oncotarget
Date: 2021-07-30

Oncotarget published this trending research paper on July 6, 2021, entitled, "Mebendazole disrupts stromal desmoplasia and tumorigenesis in two models of pancreatic cancer" by researchers from Johns Hopkins University, Baltimore, MD; Federal University of Pará, Belém, Brazil; University of North Carolina Hospitals, Women and Children Hospital, Chapel Hill, NC; Universidade Federal de São Paulo, São Paulo, Brazil.

Abstract:
The five-year survival rate for metastatic pancreatic cancer is currently only 3%, which increases to 13% with local invasion only and to 39% with localized disease at diagnosis. Here we evaluated repurposed mebendazole, an approved anthelminthic drug, to determine how mebendazole might work at the different stages of pancreatic cancer formation and progression. We asked if mebendazole could prevent initiation of pancreatic intraepithelial neoplasia precursor lesions, interfere with stromal desmoplasia, or suppress tumor growth and liver metastasis. In both the KrasLSL.G12D/+; Pdx1-Cre (KC) mouse model of caerulein-induced inflammatory pancreatitis and the KrasLSL.G12D/+; Tp53R172H/+; Pdx1-Cre (KPC) mouse model of advanced pancreatic cancer, mebendazole significantly reduced pancreas weight, dysplasia and intraepithelial neoplasia formation, compared to controls. Mebendazole significantly reduced trichrome-positive fibrotic connective tissue and α-SMA-positive activated pancreatic stellate cells that heralds fibrogenesis. In the aggressive KPC model, mebendazole significantly suppressed pancreatic tumor growth, both as an early and late intervention. Mebendazole reduced the overall incidence of pancreatic cancer and severity of liver metastasis in KPC mice. Using early models of pancreatic cancer, treatment with mebendazole resulted in less inflammation, decreased dysplasia, with the later stage model additionally showing a decreased tumor burden, less advanced tumors, and a reduction of metastasis. We conclude that mebendazole should be investigated further as a component of adjuvant therapy to slow progression and prevent metastasis, and well as for primary prevention in the highest risk patients.

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DOI - https://doi.org/10.18632/oncotarget.28014

Full text - https://www.oncotarget.com/article/28014/text/

Correspondence to - Gregory J. Riggins - griggin1@jhmi.edu

Keywords - mebendazole, pancreatic cancer, cancer prevention, metastasis, mouse models

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