ae6ac35917cd3cd74bb4027e76021955  ijms_a2018v19b10p3249.pdf
9688cbf84df6e9f2df23468d21ea5a26a147178e  ijms_a2018v19b10p3249.pdf
99f421b5672ac037bb86e895fcae1ccf37aa4b6766d6dd02229fa82470419f03  ijms_a2018v19b10p3249.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. 1.6, 2011-01-04)
 Date: 2019-02-14 17:33:14 CET
 RepresentationInformation: ijms_a2018v19b10p3249.pdf
  ReportingModule: BYTESTREAM, Rel. 1.3 (2007-04-10)
  LastModified: 2019-01-16 11:33:20 CET
  Size: 295438
  Format: bytestream
  Status: Well-Formed and valid
  SignatureMatches:
   PDF-hul
  MIMEtype: application/octet-stream
  Checksum: 715a95f0
   Type: CRC32
  Checksum: ae6ac35917cd3cd74bb4027e76021955
   Type: MD5
  Checksum: 9688cbf84df6e9f2df23468d21ea5a26a147178e
   Type: SHA-1