Journal
CANCER TREATMENT REVIEWS
Volume 70, Issue -, Pages 168-177Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ctrv.2018.09.002
Keywords
DNA Damage Repair; Biliary tract cancer; Gallbladder; Cholangiocarcinoma; Ampulla; Treatment
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Funding
- American Society of Clinical Oncology (ASCO) Conquer Cancer Foundation Young Investigator Award
- Cholangiocarcinoma Foundation Fellowship
- Christie Charity
- ENETS Centre of Excellence Fellowship Grant Award
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Biliary tract cancers (BTCs), including cholangiocarcinoma, gallbladder cancer and ampullary cancers, are poor prognosis malignancies. Most patients are diagnosed with advanced disease, when treatment is limited to palliative chemotherapy. First line chemotherapy is usually administered in the form of cisplatin and gemcitabine. Benefit from second line chemotherapy is still to be confirmed. Even though new systemic treatment targets have been recognised, especially in patients with intrahepatic cholangiocarcinoma (e.g. IDH and FGFR), there is an urgent need for novel treatment strategies. Genomic profiling of BTC is progressively becoming a reality which allows a better understanding of their biology and potential new targets. This review provides an insight into DNA Damage Repair (DDR) mechanisms, prevalence of DDR-deficient tumours in BTC, and the potential role of DDR in cancer development. Some form of DDR deficiency is expected to be present in around 25% of patients with BTC, and this knowledge could be exploited to potentially increase response to currently-available treatment strategies (chemotherapy, radiotherapy or immunotherapy). For patients with DDR-proficient tumours, drug inhibition of DDR could be instituted.
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