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- W2804007674 endingPage "713" @default.
- W2804007674 startingPage "704" @default.
- W2804007674 abstract "Defective DNA repair is a common hallmark of cancer. Homologous recombination is a DNA repair pathway of clinical interest due to the sensitivity of homologous recombination-deficient cells to poly-ADP ribose polymerase (PARP) inhibitors. The measurement of homologous recombination deficiency (HRD) in cancer is therefore vital to the appropriate design of clinical trials incorporating PARP inhibitors. However, methods to identify HRD in tumors are varied and controversial. Understanding existing and new methods to measure HRD is important to their appropriate use in clinical trials and practice. The aim of this review is to summarize the biology and clinical validation of current methods to measure HRD, to aid decision-making for patient stratification and translational research in PARP inhibitor trials. We discuss the current clinical development of PARP inhibitors, along with established indicators for HRD such as germline BRCA1/2 mutation status and clinical response to platinum-based therapy. We then examine newer assays undergoing clinical validation, including 1) somatic mutations in homologous recombination genes, 2) genomic scar assays using array-based comparative genomic hybridization (aCGH), single nucleotide polymorphism (SNP) analysis or mutational signatures derived from next-generation sequencing, 3) transcriptional profiles of HRD, and 4) phenotypic or functional assays of protein expression and localization. We highlight the strengths and weaknesses of each of these assays, for consideration during the design of studies involving PARP inhibitors." @default.
- W2804007674 created "2018-06-01" @default.
- W2804007674 creator A5008789298 @default.
- W2804007674 creator A5053619368 @default.
- W2804007674 creator A5059673967 @default.
- W2804007674 creator A5062056250 @default.
- W2804007674 date "2018-05-18" @default.
- W2804007674 modified "2023-10-14" @default.
- W2804007674 title "Biomarkers for Homologous Recombination Deficiency in Cancer" @default.
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