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Opportunities for translation: targeting DNA repair pathways in pancreatic cancer
Elaina N Maginn1, Camila H de Sousa1, Harpreet S Wasan1
1Molecular Therapy Laboratory, Department of Cancer and Surgery, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) remains one of the poorest prognosis neoplasms. It is typified by high levels of genomic aberrations and copy-number variation, intra-tumoural heterogeneity and resistance to conventional chemotherapy. Improved therapeutic options, ideally targeted against cancer-specific biological mechanisms, are urgently needed. Although induction of DNA damage and/or modulation of DNA damage response pathways are associated with the activity of a number of conventional PDAC chemotherapies, the effectiveness of this approach in the treatment of PDAC has not been comprehensively reviewed. Here, we review chemotherapeutic agents that have shown anti-cancer activity in PDAC and whose mechanisms of action involve modulation of DNA repair pathways. In addition, we highlight novel potential targets within these pathways based on the emerging understanding of PDAC biology and their exploitation as targets in other cancers.
Insights
Pancreatic ductal adenocarcinoma (PDAC) treatment needs new options. This review examines chemotherapies that target DNA repair pathways, offering insights into novel therapeutic strategies for this aggressive cancer.
Area of Science:
- Oncology
- Cancer Biology
- Genetics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with poor prognosis.
- PDAC is characterized by genomic instability, tumor heterogeneity, and chemotherapy resistance.
- Current therapeutic strategies for PDAC are limited, necessitating the development of novel treatment approaches.
Purpose of the Study:
- To review chemotherapeutic agents with demonstrated anti-cancer activity in PDAC.
- To analyze the mechanisms of action of these agents, focusing on DNA repair pathway modulation.
- To identify and highlight novel therapeutic targets within DNA repair pathways for PDAC treatment.
Main Methods:
- Comprehensive literature review of chemotherapeutic agents used in PDAC treatment.
- Analysis of studies investigating the role of DNA damage and repair in PDAC.
- Exploration of emerging PDAC biology and its implications for targeted therapy.
Main Results:
- Several conventional chemotherapies induce DNA damage or modulate DNA repair pathways in PDAC.
- The effectiveness of targeting DNA repair pathways in PDAC warrants further investigation.
- Emerging understanding of PDAC biology reveals novel targets within DNA repair mechanisms.
Conclusions:
- Modulating DNA repair pathways represents a promising therapeutic strategy for PDAC.
- Targeting DNA repair mechanisms, informed by PDAC biology, could overcome treatment resistance.
- Further research into novel targets within DNA repair pathways is crucial for improving PDAC outcomes.
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