title: Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies.
abstract: Cholangiocarcinoma (CC) encompasses a group of related but distinct malignancies whose lack of a stereotyped genetic signature makes challenging the identification of genomic landscape and the development of effective targeted therapies. Accumulated evidences strongly suggest that the remarkable genetic heterogeneity of CC may be the result of a complex interplay among different causative factors, some shared by most human cancers while others typical of this malignancy. Currently, considerable efforts are ongoing worldwide for the genetic characterization of CC, also using advanced technologies such as next-generation sequencing (NGS). Undoubtedly this technology could offer an unique opportunity to broaden our understanding on CC molecular pathogenesis. Despite this great potential, however, the high complexity in terms of factors potentially contributing to genetic variability in CC calls for a more cautionary application of NGS to this malignancy, in order to avoid possible biases and criticisms in the identification of candidate actionable targets. This approach is further justified by the urgent need to develop effective targeted therapies in this disease. A multidisciplinary approach integrating genomic, functional and clinical studies is therefore mandatory to translate the results obtained by NGS into effective targeted therapies for this orphan disease.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy.|"G. Prodi" Interdepartmental Center for Cancer Research (C.I.R.C.), University of Bologna, Bologna, Italy.|GICO- Italian Group of Cholangiocarcinoma, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Brandi
authors.affiliation: Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Farioli
authors.affiliation: "G. Prodi" Interdepartmental Center for Cancer Research (C.I.R.C.), University of Bologna, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy.|"G. Prodi" Interdepartmental Center for Cancer Research (C.I.R.C.), University of Bologna, Bologna, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), S. Orsola- Malpighi University Hospital, Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Tavolari
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000235:genetics*; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000235:genetics*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends
chemical_list: D000970:Antineoplastic Agents
keywords: cholangiocarcinoma; genetic heterogenity; targeted therapies