Olaparib is effective in combination with, and as maintenance therapy after, first-line endocrine therapy in prostate cancer cells

Molecular Oncology
Gertrud E FeiersingerFrédéric R Santer

Abstract

A number of prostate cancer (PCa)-specific genomic aberrations (denominated BRCAness genes) have been discovered implicating sensitivity to PARP inhibition within the concept of synthetic lethality. Recent clinical studies show favorable results for the PARP inhibitor olaparib used as single agent for treatment of metastatic castration-resistant PCa. Using 2D and 3D cell culture models mimicking the different treatment and progression stages of PCa, we evaluated a potential use for olaparib in combination with first-line endocrine treatments, androgen deprivation, and complete androgen blockade, and as a maintenance therapy following on from endocrine therapy. We demonstrate that the LNCaP cell line, possessing multiple aberrations in BRCAness genes, is sensitive to olaparib. Additive effects of olaparib combined with endocrine treatments in LNCaP are noted. In contrast, we find that the TMPRSS2:ERG fusion-positive cell lines VCaP and DuCaP do not show signs of synthetic lethality, but are sensitive to cytotoxic effects caused by olaparib. In consequence, additive effects of olaparib with endocrine therapy were not observable in these cell lines, showing the need for synthetic lethality in combination treatment regimens. Additi...Continue Reading

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Citations

Feb 7, 2020·NPJ Genomic Medicine·Fawz S AlHarthiMalak Abedalthagafi
Feb 3, 2021·NPJ Genomic Medicine·Fawz S AlHarthiMalak Abedalthagafi

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Methods Mentioned

BETA
chromosomal aberrations
chemical castration

Clinical Trials Mentioned

NCT01576172
NCT00749502

Software Mentioned

GraphPad
STATISTICA

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