Homologous Recombination Deficiency in Pancreatic Cancer: A Systematic Review and Prevalence Meta-Analysis

Published on Jul 1, 2021in Journal of Clinical Oncology32.956
· DOI :10.1200/JCO.20.03238
Raffaella Casolino2
Estimated H-index: 2
(Glas.: University of Glasgow),
Salvatore Paiella23
Estimated H-index: 23
+ 15 AuthorsFieke E.M. Froeling15
Estimated H-index: 15
(Glas.: University of Glasgow)
PURPOSETo analyze the prevalence of homologous recombination deficiency (HRD) in patients with pancreatic ductal adenocarcinoma (PDAC).MATERIALS AND METHODSWe conducted a systematic review and meta...
#1Milind Javle (University of Texas MD Anderson Cancer Center)H-Index: 43
#2Einat Shacham-Shmueli (Sheba Medical Center)H-Index: 8
Last. Talia Golan (Sheba Medical Center)H-Index: 20
view all 11 authors...
Importance The subtype of pancreatic ductal adenocarcinoma cancer (PDAC) with DNA damage repair (DDR) deficiency from BRCA1/2 variants has a favorable prognosis and is sensitive to platinum analogues and poly-(adenosine diphosphate-ripose) polymerase (PARP) inhibition with olaparib. Approximately 10% to 20% of patients with PDAC have DDR genetic alterations other than germline BRCA variants. This population has been termed as having BRCAness. An opportunity exists to define the clinical phenotyp...
4 CitationsSource
#1Greta Carioli (University of Milan)H-Index: 17
#2Matteo Malvezzi (University of Milan)H-Index: 38
Last. Eva Negri (University of Milan)H-Index: 153
view all 7 authors...
Background We predicted cancer mortality statistics for 2021 for the European Union (EU) and its five most populous countries plus the UK. We also focused on pancreatic cancer and female lung cancer. Materials and methods We obtained cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2015. We predicted numbers of deaths and age-standardised (world population) rates for 2021 for total cancers and 10 major cancer sites, using a joinpo...
2 CitationsSource
#1Lola Rahib (Pancreatic Cancer Action Network)H-Index: 12
#2Mackenzie R. Wehner (University of Texas MD Anderson Cancer Center)H-Index: 14
Last. Kevin T. Nead (University of Texas MD Anderson Cancer Center)H-Index: 2
view all 4 authors...
Importance Coping with the current and future burden of cancer requires an in-depth understanding of trends in cancer incidences and deaths. Estimated projections of cancer incidences and deaths will be important to guide future research funding allocations, health care planning, and health policy efforts. Objective To estimate cancer incidences and deaths in the United States to the year 2040. Design and Setting This cross-sectional study’s estimated projection analysis used population growth p...
10 CitationsSource
#1Lukas PerkhoferH-Index: 14
#2Johann GoutH-Index: 12
Last. Alexander KlegerH-Index: 26
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Complex rearrangement patterns and mitotic errors are hallmarks of most pancreatic ductal adenocarcinomas (PDAC), a disease with dismal prognosis despite some therapeutic advances in recent years. DNA double-strand breaks (DSB) bear the greatest risk of provoking genomic instability, and DNA damage repair (DDR) pathways are crucial in preserving genomic integrity following a plethora of damage types. Two major repair pathways dominate DSB repair for safeguarding the genome integrity: non-homolog...
20 CitationsSource
#1Raffaella Casolino (Glas.: University of Glasgow)H-Index: 2
#2Chiara Braconi (Glas.: University of Glasgow)H-Index: 28
Last. Talia Golan (Sheba Medical Center)H-Index: 20
view all 11 authors...
This review summarises the recent evidence on preoperative therapeutic strategies in pancreatic cancer and discusses the rationale for an imminent need for a personalized therapeutic approach in non-metastatic disease. The molecular diversity of pancreatic cancer and its influence on prognosis and treatment response, combined with the failure of "all-comer" treatments to significantly impact on patient outcomes, requires a paradigm shift towards a genomic-driven approach. This is particularly im...
4 CitationsSource
#1Talia Golan (TAU: Tel Aviv University)H-Index: 14
#1Talia Golan (Sheba Medical Center)H-Index: 20
Last. Steven Gallinger (OICR: Ontario Institute for Cancer Research)H-Index: 35
view all 28 authors...
Background and aims Homologous recombination deficiency (HRD) in pancreatic ductal adenocarcinoma (PDAC), remains poorly defined beyond germline(g) alterations in BRCA1, BRCA2 and PALB2. Methods We interrogated whole genome sequencing (WGS) data on 391 patients including 49 carriers of pathogenic variants (PVs) in gBRCA and PALB2. HRD classifiers were applied to the dataset and included: 1) the genomic instability score (GIS) used by Myriad's MyChoice HRD assay; 2) substitution base signature 3 ...
7 CitationsSource
#1Stephan Dreyer (Glas.: University of Glasgow)H-Index: 11
#2Rosie Upstill-Goddard (Glas.: University of Glasgow)H-Index: 2
Last. Owen J. Sansom (Glas.: University of Glasgow)H-Index: 90
view all 55 authors...
BACKGROUND & AIMS Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. METHODS We interrogated the transcriptome, genome, proteome, and fun...
16 CitationsSource
#1Luan Nguyen (UU: Utrecht University)H-Index: 12
#1Luan Nguyen (UU: Utrecht University)H-Index: 4
Last. Edwin Cuppen (UU: Utrecht University)H-Index: 91
view all 4 authors...
Homologous recombination deficiency (HRD) results in impaired double strand break repair and is a frequent driver of tumorigenesis. Here, we develop a genome-wide mutational scar-based pan-cancer Classifier of HOmologous Recombination Deficiency (CHORD) that can discriminate BRCA1- and BRCA2-subtypes. Analysis of a metastatic (n = 3,504) and primary (n = 1,854) pan-cancer cohort reveals that HRD is most frequent in ovarian and breast cancer, followed by pancreatic and prostate cancer. We identif...
34 CitationsSource
#1Philip A. Beer (Glas.: University of Glasgow)
#2Susanna L. Cooke (Glas.: University of Glasgow)H-Index: 28
Last. Andrew V. Biankin (Glasgow Royal Infirmary)H-Index: 73
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Through the delivery of large international projects including ICGC and TCGA, knowledge of cancer genomics is reaching saturation point. Enabling this to improve patient outcomes now requires embedding comprehensive genomic profiling into routine oncology practice. Towards this goal, this study defined the biologically and clinically relevant genomic features of adult cancer through detailed curation and analysis of large genomic datasets, accumulated literature and biomarker-driven therapeutics...
2 CitationsSource
#1Nadine Tung (Harvard University)H-Index: 76
#2Mark E. Robson (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 93
Last. Judy Garber (Harvard University)H-Index: 168
view all 25 authors...
PURPOSEOlaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved for the treatment of human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer (MBC) in...
34 CitationsSource
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