Pharmacologic reversion of Merkel cell carcinoma via CBP/p300 inhibition
CBP/p300 inhibitors suppress MCV T‑antigen expression and promote neuronal differentiation in MCC cells.
This study demonstrates that small‑molecule inhibitors of the CBP/p300 histone acetyltransferases can suppress Merkel cell polyomavirus (MCV) T‑antigen expression, arrest the cell cycle, and induce a differentiated neuronal phenotype in human Merkel cell carcinoma (MCC) cell lines. The inhibitors A‑485 and dCBP‑1 reduce viral oncogene expression, down‑regulate oncogenic pathways (E2F, MYC, mTORC1), and elevate the cell‑cycle inhibitor p27^Kip1, thereby promoting quiescence and neuronal differentiation.
Targeting the CBP/p300 co‑activators offers a novel therapeutic strategy that converts aggressive MCC tumors into a quiescent, differentiated state, potentially reducing tumor burden and improving patient outcomes.
Evidence level: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.
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