title: Autocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma.
abstract: Resistance to conventional chemotherapeutic agents, a typical feature of cholangiocarcinoma, prevents the efficacy of the therapeutic arsenal usually used to combat malignancy in humans. Mechanisms of chemoresistance by neoplastic cholangiocytes include evasion of drug-induced apoptosis mediated by autocrine and paracrine cues released in the tumor microenvironment. Here, recent evidence regarding molecular mechanisms of chemoresistance is reviewed, as well as associations between well-developed chemoresistance and activation of the cancer stem cell compartment. It is concluded that improved understanding of the complex interplay between apoptosis signaling and the promotion of cell survival represent potentially productive areas for active investigation, with the ultimate aim of encouraging future studies to unveil new, effective strategies able to overcome current limitations on treatment.
authors.affiliation: School of Medicine and Surgery, University of Milan-Bicocca, 20900 MB Monza, Italy. massimiliano.cadamuro@unimib.it.|International Center for Digestive Health (ICDH), University of Milan-Bicocca, 20900 MB Monza, Italy. massimiliano.cadamuro@unimib.it.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cadamuro
authors.affiliation: School of Medicine and Surgery, University of Milan-Bicocca, 20900 MB Monza, Italy. s.brivio3@campus.unimib.it.
authors.forename: Simone
authors.initials: S
authors.lastname: Brivio
authors.affiliation: Digestive Disease Section, Yale University School of Medicine, New Haven, CT 06520, USA. carlo.spirli@yale.edu.
authors.forename: Carlo
authors.initials: C
authors.lastname: Spirli
authors.affiliation: The School of Medicine, Royal Derby Hospital, University of Nottingham, Derby DE22 3NE, UK. ruthjop@hotmail.co.uk.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Joplin
authors.affiliation: School of Medicine and Surgery, University of Milan-Bicocca, 20900 MB Monza, Italy. mario.strazzabosco@yale.edu.|International Center for Digestive Health (ICDH), University of Milan-Bicocca, 20900 MB Monza, Italy. mario.strazzabosco@yale.edu.|Digestive Disease Section, Yale University School of Medicine, New Haven, CT 06520, USA. mario.strazzabosco@yale.edu.
authors.forename: Mario
authors.initials: M
authors.lastname: Strazzabosco
authors.affiliation: International Center for Digestive Health (ICDH), University of Milan-Bicocca, 20900 MB Monza, Italy. luca.fabris@unipd.it.|Digestive Disease Section, Yale University School of Medicine, New Haven, CT 06520, USA. luca.fabris@unipd.it.|Department of Molecular Medicine, University of Padova School of Medicine, 35131 PD Padova, Italy. luca.fabris@unipd.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Fabris
mesh_terms: D019898:Autocrine Communication; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D019899:Paracrine Communication; D017154:Stromal Cells / Q000473:pathology
keywords: apoptosis; cancer stem cells; liver cancer; morphogens; tumor reactive stroma