Role of drug-dependent transporter modulation on the chemosensitivity of cholangiocarcinoma.
Por:
Urtasun N, Boces-Pascual C, Boix L, Bruix J, Pastor-Anglada M and Perez-Torras S
Publicada:
27 oct 2017
Ahead of Print:
6 oct 2017
Categoría:
Oncology
Resumen:
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.
Filiaciones:
Urtasun N:
Molecular 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
Oncology Program, CIBER ehd, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, Barcelona, Spain
Boces-Pascual C:
Molecular 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
Boix L:
Oncology Program, CIBER ehd, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, Barcelona, Spain
Barcelona 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
Bruix J:
Oncology Program, CIBER ehd, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, Barcelona, Spain
Barcelona 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
Pastor-Anglada M:
Molecular 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
Oncology Program, CIBER ehd, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, Barcelona, Spain
Perez-Torras S:
Molecular 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
Oncology Program, CIBER ehd, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, Barcelona, Spain
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