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Hépato-Gastro & Oncologie Digestive

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BRCA 1/2 mutations and PARP inhibitors in pancreatic cancer: The POLO study and after? Volume 28, issue 6, Juin 2021

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Authors
1 Hôpital Paul-Brousse, Université de Paris-Saclay, service d’oncologie digestive et médicale, 94800 Villejuif
2 Hôpital Beaujon, Université de Paris, Unité d’oncologie hépatique, 92110 Clichy
* Correspondance

A germline mutation of BRCA1 or BRCA2 genes is identified in 5% to 7 % of pancreatic cancer patients. Due to the altered function of these genes, DNA break repair then relies on an alternate pathway (PARP), the inhibition of which can then lead to cell death. The phase 3 POLO study showed that the PARP inhibitor olaparib, administered as maintenance treatment in metastatic pancreatic cancer patients with BRCA1/2 germline mutation and who's tumor has previously been controlled using a platinum-based chemotherapy, can significantly increase the tumor control time. This study generated criticisms and raised questions about the transposition of efficiency against somatic mutations in BRCA1/2 genes but also in other DNA repair genes. The predictability of the efficacy of PARP inhibitors in these tumors and the role of their combination with immunotherapies should be investigated. The interest in therapies targeted at genetic abnormalities in pancreatic cancers (BRCA 1/2 but also NTRK, NRG1, MMR…) is relaunched.