Cancers, Vol. 11, Pages 751: PARP Inhibition Increases the Response to Chemotherapy in Uveal Melanoma

Cancers, Vol. 11, Pages 751: PARP Inhibition Increases the Response to Chemotherapy in Uveal Melanoma Cancers doi: 10.3390/cancers11060751 Authors: de Koning Decaudin El Botty Nicolas Carita Schuller Ouine Cartier Naguez Fleury Cooke Wylie Smith Marangoni Gentien Meseure Mariani Cassoux Piperno-Neumann Roman-Roman Némati Uveal melanoma (UM) remains without effective therapy at the metastatic stage, which is associated with BAP-1 (BRCA1 associated protein) mutations. However, no data on DNA repair capacities in UM are available. Here, we use UM patient-derived xenografts (PDXs) to study the therapeutic activity of the PARP inhibitor olaparib, alone or in combination. First, we show that the expression and the activity of PARP proteins is similar between the PDXs and the corresponding patient’s tumors. In vivo experiments in the PDX models showed that olaparib was not efficient alone, but significantly increased the efficacy of dacarbazine. Finally, using reverse phase protein arrays and immunohistochemistry, we identified proteins involved in DNA repair and apoptosis as potential biomarkers predicting response to the combination of olaparib and dacarbazine. We also observed a high increase of phosphorylated YAP and TAZ proteins after dacarbazine + olaparib treatment. Our results suggest that PARP inhibition in combination with the alkylating agent dacarbazine could be of clinical interest for U...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research