Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma.

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Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma.

Head Neck. 2018 Mar 23;:

Authors: Ferrarotto R, Cardnell R, Su S, Diao L, Eterovic AK, Prieto V, Morrisson WH, Wang J, Kies MS, Glisson BS, Byers LA, Bell D

Abstract
BACKGROUND: Patients with metastatic Merkel cell carcinoma are treated similarly to small cell lung cancer (SCLC). Poly ADP-ribose polymerase-1 (PARP1) is overexpressed in SCLC and response to PARP inhibitors have been reported in patients with SCLC. Our study explores PARP as a therapeutic target in Merkel cell carcinoma.
METHODS: We evaluated PARP1 expression and Merkel cell polyomavirus (MCPyV) in 19 patients with Merkel cell carcinoma. Target exome-sequencing was performed in 14 samples. Sensitivity to olaparib was tested in 4 Merkel cell carcinoma cell lines.
RESULTS: Most Merkel cell carcinomas (74%) express PARP1 at high levels. Mutations in DNA-damage repair genes were identified in 9 samples (64%), occurred exclusively in head neck primaries, and correlated with TP53/RB1 mutations. The TP53/RB1 mutations were more frequent in MCPyV-negative tumors. Sensitivity to olaparib was seen in the Merkel cell carcinoma line with highest PARP1 expression.
CONCLUSION: Based on PARP1 overexpression, DNA-damage repair gene mutations, platinum sensitivity, and activity of olaparib in a Merkel cell carcinoma line, clinical trials with PARP inhibitors are warranted in Merkel cell carcinoma.

PMID: 29570891 [PubMed - as supplied by publisher]

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