Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies

Giovanni Brandi _, Andrea Farioli, Annalisa Astolfi, Guido Biasco and Simona Tavolari

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Oncotarget. 2015; 6:14744-14753. https://doi.org/10.18632/oncotarget.4539

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Giovanni Brandi1,2,5, Andrea Farioli3, Annalisa Astolfi2, Guido Biasco1,2 and Simona Tavolari1,4

1 Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy

2 “G. Prodi” Interdepartmental Center for Cancer Research (C.I.R.C.), University of Bologna, Bologna, Italy

3 Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Bologna, Italy

4 Center for Applied Biomedical Research (C.R.B.A.), S. Orsola- Malpighi University Hospital, Bologna, Italy

5 GICO- Italian Group of Cholangiocarcinoma, Italy

Correspondence to:

Giovanni Brandi, email:

Keywords: cholangiocarcinoma, genetic heterogenity, targeted therapies

Received: March 18, 2015 Accepted: June 11, 2015 Published: June 19, 2015


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.

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