Is it time to split strategies to treat homologous recombinant deficiency in pancreas cancer? Journal Article
| Authors: | Teo, M. Y.; O'Reilly, E. M. |
| Article Title: | Is it time to split strategies to treat homologous recombinant deficiency in pancreas cancer? |
| Abstract: | Pancreatic cancer is a highly lethal malignancy which tends to present with late stage disease. To date, identification of oncogenic drivers and aberrations has not led to effective targeted therapy. Approximately 5-15% of pancreatic cancer has an inheritable component. In fact, pancreatic adenocarcinoma is now recognized as a BRCA1/2-related cancer. Germline BRCA1/2 mutations can be found in up to 3.6-7% of unselected pancreatic cancer patients although the rates are significantly higher amongst patients with Ashkenazi Jewish ancestry. Germline mutations of other components of DNA repair and homologous recombination have also been identified although at much lower frequency. Large sequencing efforts have further identified somatic mutations in these genes in a small subset of pancreatic cancers. Small series and case reports have suggested that pancreatic cancers harboring BRCA1/2 or other homologous repair gene mutations demonstrate enhanced response to platinum-based chemotherapy although this has not been prospectively validated. Clinical trials with poly (ADP-ribose) polymerase (PARP) inhibitors as monotherapy or in combination with chemotherapy in different clinical settings are currently on-going. A subtype of pancreatic adenocarcinoma as characterized by deficiency in homologous recombination exists although the optimal management strategy remains to be fully elucidated. |
| Keywords: | dna repair; genomic instability; pancreatic cancer; brca1; brca2; ovarian-cancer; prostate-cancer; phase-ii; strand break repair; polymorphisms; dna-damage response; clinical characteristics; brca mutation carriers; repair gene; homologous recombination deficiency; (hrd); ribose polymerase inhibitors |
| Journal Title: | Journal of Gastrointestinal Oncology |
| Volume: | 7 |
| Issue: | 5 |
| ISSN: | 2078-6891 |
| Publisher: | Pioneer Bioscience Publishing Company |
| Date Published: | 2016-10-01 |
| Start Page: | 738 |
| End Page: | 749 |
| Language: | English |
| ACCESSION: | WOS:000392546900008 |
| DOI: | 10.21037/jgo.2016.05.04 |
| PROVIDER: | wos |
| PMCID: | PMC5056255 |
| PUBMED: | 27747088 |
| Notes: | Review -- Source: Wos |
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