TY - JOUR
T1 - Targeted Therapies for Perihilar Cholangiocarcinoma
AU - Gray, Simon
AU - Lamarca, Angela
AU - Edeline, Julien
AU - Klümpen, Heinz-Josef
AU - Hubner, Richard A.
AU - McNamara, Mairéad G.
AU - Valle, Juan W.
N1 - Funding Information: Funding: The salary for Simon Gray is supported by The Christie Charity. Angela Lamarca received funding from The Christie Charity and the European Union’s Horizon 2020 Research and Innovation Programme [grant number 825510, ESCALON]. This publication is based upon work of COST Action CA18122—European Cholangiocarcinoma Network; supported by COST (European Cooperation in Science and Technology; www.cost.eu (accessed on 6 March 2022)), a funding agency for research and innovation networks. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Perihilar cholangiocarcinoma (pCCA) is the anatomical sub-group of biliary tract cancer (BTC) arising between the second-order intrahepatic bile ducts and the cystic duct. Together with distal and intrahepatic cholangiocarcinoma (dCCA and iCCA; originating distal to, and proximal to this, respectively), gallbladder cancer (GBC) and ampulla of Vater carcinoma (AVC), these clini-copathologically and molecularly distinct entities comprise biliary tract cancer (BTC). Most pCCAs are unresectable at diagnosis, and for those with resectable disease, surgery is extensive, and recurrence is common. Therefore, the majority of patients with pCCA will require systemic treatment for advanced disease. The prognosis with cytotoxic chemotherapy remains poor, driving interest in therapies targeted to the molecular nature of a given patient’s cancer. In recent years, the search for efficacious targeted therapies has been fuelled both by whole-genome and epigenomic studies, looking to uncover the molecular landscape of CCA, and by specifically testing for aberrations where established therapies exist in other indications. This review aims to provide a focus on the current molecular characterisation of pCCA, targeted therapies applicable to pCCA, and future di-rections in applying personalised medicine to this difficult-to-treat malignancy.
AB - Perihilar cholangiocarcinoma (pCCA) is the anatomical sub-group of biliary tract cancer (BTC) arising between the second-order intrahepatic bile ducts and the cystic duct. Together with distal and intrahepatic cholangiocarcinoma (dCCA and iCCA; originating distal to, and proximal to this, respectively), gallbladder cancer (GBC) and ampulla of Vater carcinoma (AVC), these clini-copathologically and molecularly distinct entities comprise biliary tract cancer (BTC). Most pCCAs are unresectable at diagnosis, and for those with resectable disease, surgery is extensive, and recurrence is common. Therefore, the majority of patients with pCCA will require systemic treatment for advanced disease. The prognosis with cytotoxic chemotherapy remains poor, driving interest in therapies targeted to the molecular nature of a given patient’s cancer. In recent years, the search for efficacious targeted therapies has been fuelled both by whole-genome and epigenomic studies, looking to uncover the molecular landscape of CCA, and by specifically testing for aberrations where established therapies exist in other indications. This review aims to provide a focus on the current molecular characterisation of pCCA, targeted therapies applicable to pCCA, and future di-rections in applying personalised medicine to this difficult-to-treat malignancy.
KW - biliary tract cancer
KW - cholangiocarcinoma
KW - extrahepatic
KW - pCCA
KW - perihilar
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85127452038&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers14071789
DO - https://doi.org/10.3390/cancers14071789
M3 - Review article
C2 - 35406560
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 7
M1 - 1789
ER -