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PARP Inhibitors in Biliary Tract Cancer: A New Kid on the Block?
Angela Dalia Ricci1, Alessandro Rizzo1, Chiara Bonucci1
1Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi Hospital, University of Bologna, 40128 Bologna, Italy.
Abstract:
Poly adenosine diphosphate-ribose polymerase inhibitors (PARPi) represent an effective therapeutic strategy for cancer patients harboring germline and somatic aberrations in DNA damage repair (DDR) genes. BRCA1/2 mutations occur at 1-7% across biliary tract cancers (BTCs), but a broader spectrum of DDR gene alterations is reported in 28.9-63.5% of newly diagnosed BTC patients. The open question is whether alterations in genes that are well established to have a role in DDR could be considered as emerging predictive biomarkers of response to platinum compounds and PARPi. Currently, data regarding PARPi in BTC patients harboring BRCA and DDR mutations are sparse and anecdotal; nevertheless, a variety of clinical trials are testing PARPi as monotherapy or in combination with other anticancer agents. In this review, we provide a comprehensive overview regarding the genetic landscape of DDR pathway deficiency, state of the art and future therapeutic implications of PARPi in BTC, looking at combination strategies with immune-checkpoint inhibitors and other anticancer agents in order to improve survival and quality of life in BTC patients.
Insights
Poly adenosine diphosphate-ribose polymerase inhibitors (PARPi) show promise for biliary tract cancers (BTCs) with DNA damage repair (DDR) gene alterations. Further research into PARPi and combination therapies may improve patient survival.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Poly adenosine diphosphate-ribose polymerase inhibitors (PARPi) are effective for cancers with DNA damage repair (DDR) gene aberrations.
- Biliary tract cancers (BTCs) show varying frequencies of BRCA1/2 mutations and broader DDR gene alterations.
Purpose of the Study:
- To review the genetic landscape of DDR deficiency in BTC.
- To explore the therapeutic implications and combination strategies of PARPi in BTC.
Main Methods:
- Comprehensive literature review of genetic alterations in DDR pathways.
- Analysis of current and emerging PARPi clinical trials in BTC.
- Exploration of combination therapies including immune-checkpoint inhibitors.
Main Results:
- A significant proportion of BTC patients harbor DDR gene alterations, suggesting potential for PARPi therapy.
- Data on PARPi efficacy in BTC with DDR mutations are limited but growing.
- Clinical trials are actively investigating PARPi as monotherapy and in combination regimens.
Conclusions:
- DDR gene alterations represent potential predictive biomarkers for PARPi and platinum compound response in BTC.
- PARPi, especially in combination strategies, holds promise for improving outcomes in BTC patients.
- Further research is crucial to optimize PARPi use and combination therapies for enhanced survival and quality of life in BTC.
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