Role of drug-dependent transporter modulation on the chemosensitivity of cholangiocarcinoma
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Nerea Urtasun1,2, Clara Boces-Pascual1, Loreto Boix2,3, Jordi Bruix2,3, Marçal Pastor-Anglada1,2 and Sandra Pérez-Torras1,2
1Molecular Pharmacology and Experimental Therapeutics (MPET), Section Biochemistry and Molecular Pharmacology, Department of Biochemistry and Molecular Biomedicine, Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain
2Oncology Program, CIBER ehd, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, Barcelona, Spain
3Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic of Barcelona, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain
Sandra Pérez-Torras, email: [email protected]
Keywords: transporter, cholangiocarcinoma, gemcitabine, cisplatin, chemoresistance
Received: February 07, 2017 Accepted: August 27, 2017 Published: October 06, 2017
Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with limited therapeutic options. Curative therapy is limited to surgery whereas chemotherapy treatments are the election option for unresectable or metastatic cholangiocarcinoma. Cisplatin plus gemcitabine is the reference chemotherapy regimen, albeit the contribution to the median overall survival barely reaches one year. Drug transporters are undoubtedly a limiting step for drug bioavailability and have been clearly related to chemoresistance. Several members of the SoLute Carrier (SLC) superfamily involved in the uptake of anticancer drugs used to treat cholangiocarcinoma are downregulated in these tumors. This study shows the increase in the expression of specific drug transporters exerted by cisplatin treatment thereby enhancing their transport activity. Combination treatments of cisplatin with selected drugs as gemcitabine and sorafenib take in by these transporters at the desired combination schedule induced synergy. These data support the concept that proper administration pattern could favor treatment outcome.
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