Role of molecular genetics in the clinical management of cholangiocarcinoma

ESMO Open. 2022 Jun;7(3):100505. doi: 10.1016/j.esmoop.2022.100505. Epub 2022 Jun 10.

Abstract

The incidence of cholangiocarcinoma (CCA) has steadily increased during the past 20 years, and mortality is increasing. The majority of patients with CCA have advanced or metastatic disease at diagnosis, and treatment options for unresectable disease are limited, resulting in poor prognosis. However, recent identification of targetable genomic alterations has expanded treatment options for eligible patients. Given the importance of early and accurate diagnosis in optimizing patient outcomes, this review discusses best practices in CCA diagnosis, with a focus on categorizing molecular genetics and available targeted therapies. Imaging and staging of CCAs are discussed, as well as recommended biopsy collection techniques, and molecular and genomic profiling methodologies, which have become increasingly important as molecular biomarker data accumulate. Approved agents targeting actionable genomic alterations specifically in patients with CCA include ivosidenib for tumors harboring IDH1 mutations, and infigratinib and pemigatinib for those with FGFR2 fusions. Other agents currently under development in this indication have shown promising results, which are presented here.

Keywords: FGFR2; IDH1; extrahepatic cholangiocarcinoma; genomic profile; intrahepatic cholangiocarcinoma.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Duct Neoplasms* / drug therapy
  • Bile Duct Neoplasms* / genetics
  • Bile Duct Neoplasms* / pathology
  • Bile Ducts, Intrahepatic / pathology
  • Cholangiocarcinoma* / drug therapy
  • Cholangiocarcinoma* / genetics
  • Cholangiocarcinoma* / pathology
  • Humans
  • Molecular Biology