Activation of Wnt signaling promotes olaparib resistant ovarian cancer.

Sequencing of olaparib-resistant PEO1 derivatives (C4, C5, C10 and C18) and parental PEO1 (P1 and P2) cells was performed in order to determine mechanisms of acquired resistance in the resistant cell lines. PEO1 parental cell lines were authenticated prior to sequencing. PEO1 parental were confirmed to be BRCA2-mutated (5139C>G). Olaparib PEO1 resistant cells were generated through a step-wise escalation of olaparib (10nM to 8uM olaparib). In olaparib resistant lines an increase canonical Wnt signaling and loss of of non-canonical Wnt signaling was observed. Overall design: Sequencing of olaparib-resistant PEO1 derivatives (C4, C5, C10, and C18) and parental PEO1 cells was performed in order to determine mecahnisms of acquired resistance.

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Yamamoto TM, McMellen A, Watson ZL, Aguilera J, Ferguson R, Nurmemmedov E, Thakar T, Moldovan GL, Kim H, Cittelly DM, Joglar AM, Brennecke EP, Wilson H, Behbakht K, Sikora MJ, Bitler BG