ae6ac35917cd3cd74bb4027e76021955 pmc_30347758.pdf 9688cbf84df6e9f2df23468d21ea5a26a147178e pmc_30347758.pdf 99f421b5672ac037bb86e895fcae1ccf37aa4b6766d6dd02229fa82470419f03 pmc_30347758.pdf Title: Translational Research Opportunities Regarding Homologous Recombination in Ovarian Cancer Subject: Homologous recombination (HR) is a DNA repair pathway that is deficient in 50% of high-grade serous ovarian carcinomas (HGSOC). Deficient HR (DHR) constitutes a therapeutic opportunity for these patients, thanks to poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi; olaparib, niraparib, and rucaparib are already commercialized). Although initially, PARPi were developed for patients with BRCA1/2 mutations, robust clinical data have shown their benefit in a broader population without DHR. This breakthrough in daily practice has raised several questions that necessitate further research: How can populations that will most benefit from PARPi be selected? At which stage of Ovarian Cancer should PARPi be used? Which strategies are reasonable to overcome PARPi resistance? In this paper, we present a summary of the literature and discuss the present clinical research involving PARPi (after reviewing ` `%%%`#`&12_`__~~~) from a translational perspective. Research into the functional biomarkers of DHR and clinical trials testing PARPi benefits as first-line setting or rechallenge are currently ongoing. Additionally, in the clinical setting, only secondary restoring mutations of BRCA1/2 have been identified as events inducing resistance to PARPi. The clinical frequency of this and other mechanisms that have been described in preclinics is unknown. It is of great importance to study mechanisms of resistance to PARPi to guide the clinical development of drug combinations. Keywords: Ovarian Cancer; high-grade serous Ovarian Cancer; deficient homologous recombination; PARP inhibitors; BRCA1; BRCA2; mechanisms of resistance Author: Margarita Romeo, Juan Carlos Pardo, Anna Martínez-Cardús, Eva Martínez-Balibrea, Vanesa Quiroga, Sergio Martínez-Román, Francesc Solé, Mireia Margelí and Ricard Mesía Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Fri Oct 19 15:24:56 2018 CEST ModDate: Fri Oct 19 15:24:56 2018 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 295438 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- RFLFOT+URWPalladioL-Ital Type 1 Custom yes yes no 94 0 EZRPZF+URWPalladioL-Bold Type 1 Custom yes yes no 95 0 OSMCID+VnURWPalladioL-Bold Type 1 Custom yes yes no 96 0 FSYUXP+URWPalladioL-Roma Type 1 Custom yes yes no 97 0 OGLZWV+VnURWPalladioL Type 1 Custom yes yes no 98 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 103 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 104 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 123 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 124 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 125 0 SAUAIP+CMSY10 Type 1 Builtin yes yes no 357 0 ARLQUR+EURM10 Type 1 Builtin yes yes no 388 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-01-19 05:52:07 CET RepresentationInformation: pmc_30347758.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2020-08-03 03:47:26 CEST Size: 295438 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false 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Rect: 372, 483, 408, 493 Annotation: Subtype: Link Rect: 140, 444, 178, 454 Annotation: Subtype: Link Rect: 184, 444, 220, 454 Annotation: Subtype: Link Rect: 438, 417, 475, 428 Annotation: Subtype: Link Rect: 481, 417, 516, 428 Annotation: Subtype: Link Rect: 350, 378, 388, 390 Annotation: Subtype: Link Rect: 394, 378, 430, 390 Annotation: Subtype: Link Rect: 398, 340, 436, 351 Annotation: Subtype: Link Rect: 442, 340, 478, 351 Annotation: Subtype: Link Rect: 100, 276, 137, 286 Annotation: Subtype: Link Rect: 143, 276, 179, 286 Annotation: Subtype: Link Rect: 397, 224, 434, 235 Annotation: Subtype: Link Rect: 302, 185, 340, 196 Annotation: Subtype: Link Rect: 346, 185, 382, 196 Annotation: Subtype: Link Rect: 100, 121, 137, 131 Annotation: Subtype: Link Rect: 76, 79, 166, 110 Annotation: Subtype: Link Rect: 234, 73, 424, 84 Checksum: 715a95f0 Type: CRC32 Checksum: ae6ac35917cd3cd74bb4027e76021955 Type: MD5 Checksum: 9688cbf84df6e9f2df23468d21ea5a26a147178e Type: SHA-1 Checksum: 99f421b5672ac037bb86e895fcae1ccf37aa4b6766d6dd02229fa82470419f03 Type: SHA-256