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Review

Molecular-driven treatment for biliary tract cancer: the promising turning point

ORCID Icon, , , , , , , , , , , , , , & show all
Pages 1253-1264 | Received 06 Jun 2021, Accepted 16 Sep 2021, Published online: 24 Sep 2021
 

ABSTRACT

Introduction

In the past, targeted therapies have not shown positive results as they have been used without adequate molecular selection of patients with biliary tract cancer (BTC). This has led to an expansion of research on characteristics and molecular selection to identify new effective strategies in this setting. Improved knowledge of the molecular biology of these neoplasms has highlighted their extraordinary heterogeneity and has made it possible to identify targetable gene alterations, including fibroblast growth factor receptor (FGFR) 2 gene fusions, and isocitrate dehydrogenase (IDH) mutations. The FDA recently approved ivosidenib and pemigatinib for the treatment of BTCs.

Areas covered

We review data in the literature regarding targeted therapies for the treatment of BTCs, as well as on the prospects deriving from the extraordinary molecular heterogeneity of these neoplasms.

Expert opinion

At present, it is essential to evaluate the expression of the genetic alterations expressed by these neoplasms to offer patients an increasingly personalized therapeutic approach. Studies are needed to better define the limits and potentials of targeted therapies and their role in the therapeutic algorithm to improve the poor prognosis of these patients.

Article highlights

  • In the past, targeted therapies have not shown positive results as they have been used without adequate molecular selection of patients.

  • BTCs consist of a group of highly heterogeneous malignancies characterized by genomic differences among tumors from different anatomic sites.

  • Molecular classification may represent the key to improve clinical outcomes through personalized therapy.

  • The approval of pemigatinib and ivosedanib by FDA represents a turning point for the clinical history of these tumors.

  • Researchers should seek to fill in the gaps regarding the tests used to evaluate the molecular characterization, the mechanisms of resistance of targeted therapies, and the role of TME in the oncogenesis and development of these neoplasms.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

MS, M Puzzoni, and M Persano contributed conception of the manuscript; M Persano and M Puzzoni wrote sections of the manuscript; CD drew the figures; PZ, VP, and EL contributed design of the manuscript. MS, A Pretta, GP, DS, EC, A Parrino, NL, SM, MD, and MM contributed to manuscript revision, read and approved the submitted version.

Additional information

Funding

This paper received no funding.

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