Treatment options for biliary tract cancer: unmet needs, new targets and opportunities from both physicians' and patients' perspectives

Future Oncol. 2024;20(20):1435-1450. doi: 10.1080/14796694.2024.2340959. Epub 2024 May 30.

Abstract

Biliary tract cancer (BTC) is a rare cancer with poor prognosis, characterized by considerable pathophysiological and molecular heterogeneity. While this makes it difficult to treat, it also provides targeted therapy opportunities. Current standard-of-care is chemotherapy ± immunotherapy, but several targeted agents have recently been approved. The current investigational landscape in BTC emphasizes the importance of biomarker testing at diagnosis. MDM2/MDMX are important negative regulators of the tumor suppressor p53 and provide an additional target in BTC (∼5-8% of tumors are MDM2-amplified). Brigimadlin (BI 907828) is a highly potent MDM2-p53 antagonist that has shown antitumor activity in preclinical studies and promising results in early clinical trials; enrollment is ongoing in a potential registrational trial for patients with BTC.

Keywords: BI 90782823; MDM2–p53; biliary tract cancer; brigimadlin; plain-language summary; targeted therapy.

Plain language summary

[Box: see text].

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biliary Tract Neoplasms* / drug therapy
  • Biliary Tract Neoplasms* / therapy
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Humans
  • Immunotherapy / methods
  • Molecular Targeted Therapy* / methods
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-mdm2
  • Antineoplastic Agents
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins
  • MDM4 protein, human
  • Cell Cycle Proteins

Grants and funding