Emerging treatment evolutions and integrated molecular characteristics of biliary tract cancers

Cancer Sci. 2021 Dec;112(12):4819-4833. doi: 10.1111/cas.15139. Epub 2021 Oct 6.


Biliary tract cancers (BTCs) consist of a group of highly heterogeneous malignancies that are characterized by genomic differences among tumors from different anatomic sites. The current treatment for BTC includes surgery, chemotherapy, target therapy, and immunotherapy. Although surgery remains the primary option for localized disease, representing the only potential curative treatment, a high risk of recurrence cannot be neglected. Chemotherapy has been considered the standard of care for both advanced and metastatic disease and in adjuvant settings. However, drug resistance is a major obstacle associated with chemotherapy. The development of genetic testing technologies, including next-generation sequencing, has opened the door for the identification of drug targets and candidate molecules. A series of preclinical studies has demonstrated the role of gene mutations, abnormal signaling pathways, and immunosuppression in the pathogenesis of BTC, laying the foundation for the application of targeted therapy and immunotherapy. A variety of molecularly targeted agents, including pemigatinib, have shown promising survival benefits in patients with advanced disease. The rapidly evolving role of multimodal therapy represents the subject of this review.

Keywords: biliary tract cancers; clinical trials; immunotherapy; molecular characterization; targeted therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biliary Tract Neoplasms / genetics
  • Biliary Tract Neoplasms / therapy*
  • Clinical Trials as Topic
  • Combined Modality Therapy / methods*
  • Digestive System Surgical Procedures
  • Gene Regulatory Networks* / drug effects
  • Humans
  • Molecular Targeted Therapy
  • Precision Medicine
  • Radiotherapy


  • Antineoplastic Agents