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- W4366088045 abstract "Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with a poor prognosis. MCC has been reported to be a chemotherapy-sensitive tumor; however, advanced MCC is likely to recur. Although the development of novel therapeutic strategies against MCC has been desired, available preclinical models are limited. This study aims to establish a preclinical research model for MCC, toward the development of novel therapies. We transplanted cutaneous MCC tissue from a human patient into immunodeficient NOD/Scid mice, let it grow as patient-derived xenograft (PDX) tumors, and then re-transplanted the tumorous PDX tissue into further immunodeficient NOD/Scid mouse generations. Histopathologically, these PDX tumors were positive for the Merkel cell carcinoma polyomavirus (MCPyV), which was consistent with the patient’s tumors. The pathogenic mutation RB1 p.E323* was detected in both the patient’s tumors and the PDX tumors. As in vivo preclinical treatments, we administered cisplatin, etoposide, docetaxel, or eribulin to the tumor-bearing immunodeficient mice. The tumors responded well only to the eribulin therapy. Clinical samples from 19 MCC patients revealed the MCC tumors to have either MCPyV infection or a loss of protein expression of certain tumor suppressors (p53 and RB1). Reportedly, the anti-tumor activity of eribulin tends to be greater in tumors that harbor disrupted tumor suppressors, which is consistent with our preclinical results. In conclusion, the present therapeutic experiments revealed in vivo tumor growth inhibition from eribulin administration. Also, our novel PDX model could be useful for developing further novel therapies." @default.
- W4366088045 created "2023-04-19" @default.
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- W4366088045 date "2023-05-01" @default.
- W4366088045 modified "2023-10-16" @default.
- W4366088045 title "240 Eribulin has anti-tumor activity in a preclinical model of merkel cell carcinoma" @default.
- W4366088045 doi "https://doi.org/10.1016/j.jid.2023.03.244" @default.
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