The role of PARP inhibitors in germline BRCA-associated pancreatic ductal adenocarcinoma Review
| Authors: | Moffat, G. T.; O’Reilly, E. M. |
| Review Title: | The role of PARP inhibitors in germline BRCA-associated pancreatic ductal adenocarcinoma |
| Abstract: | Pancreatic ductal adenocarcinoma (PDAC) is an aggres-sive malignancy that remains a challenge to treat. In pursuit of personalized medicine, researchers continue active exploration of the genetic and molecular framework of PDAC to apply novel therapeutics and enhance outcomes. In patients who have PDAC, germline mutations—such as those in the BRCA1/2 and PALB2 genes—are predominantly associated with the DNA damage response and repair pathway. On the basis of studies completed in patients with BRCA-mutated advanced breast and ovarian cancer, the poly(ADP-ribose) polymerase (PARP) inhibitors have been evaluated for safety, tolerability, and efficacy in patients with advanced PDAC who are carrying germline BRCA gene mutations. Results have demonstrated meaningful activity and identified BRCA as a predictive and targetable biomarker in PDAC, and have also identified the role of olaparib as a maintenance therapy in PDAC. On the basis of the principle of synthetic lethality, and to avert resistance to PARP inhibitors, clinical trials of combination therapy with PARP inhibitors and platinum-based chemotherapy have been conducted with an early signal. As we continue to explore the role of PARP inhibitors in the management of PDAC, recent clinical trials are studying the effectiveness of PARP inhibi-tors in combination with immunotherapy, targeted inhibitors, and angiogenesis inhibitors. The next steps are to understand the role of PARP inhibitors beyond germline BRCA in other homologous recombination repair gene mutations and in other subgroups of patients with PDAC. © 2020, Millennium Medical Publishing, Inc. All rights reserved. |
| Keywords: | signal transduction; cancer chemotherapy; protein expression; treatment response; gene mutation; overall survival; constipation; fatigue; cisplatin; fluorouracil; diarrhea; drug efficacy; gemcitabine; dna damage; homologous recombination; dna repair; germline; progression free survival; quality of life; gene expression; nausea; prevalence; maintenance therapy; brca1 protein; cancer therapy; irinotecan; abdominal pain; tumor suppressor gene; genomic instability; folinic acid; pancreas adenocarcinoma; platinum; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; pancreatic cancer; oxaliplatin; tumor gene; brca; olaparib; personalized medicine; tumor microenvironment; molecularly targeted therapy; phase 2 clinical trial (topic); phase 1 clinical trial (topic); germline mutation; veliparib; niraparib; rucaparib; human; article; loss of appetite; poly(adp-ribose) polymerase inhibitors; partner and localizer of brca2 |
| Journal Title: | Clinical Advances in Hematology & Oncology |
| Volume: | 18 |
| Issue: | 3 |
| ISSN: | 1543-0790 |
| Publisher: | Millennium Medical Publishing, Inc |
| Date Published: | 2020-03-01 |
| Start Page: | 168 |
| End Page: | e181 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 32609666 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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