The molecular mechanisms and targeting strategies of transcription factors in cholangiocarcinoma

Expert Opin Ther Targets. 2022 Sep;26(9):781-789. doi: 10.1080/14728222.2022.2137020. Epub 2022 Oct 19.

Abstract

Introduction: Cholangiocarcinoma consists of a cluster of malignant biliary tumors that tend to have a poor prognosis, ranking as the second most prevalent type of liver cancer, and their incidence rate has increased globally recently. The high-frequency driving mutations of cholangiocarcinoma, such as KRAS/IDH1/ARID1A/P53, imply the epigenetic instability of cholangiocarcinoma, leading to the dysregulation of various related transcription factors, thus affecting the occurrence and development of cholangiocarcinoma. Increasingly evidence indicates that the high heterogeneity and malignancy of cholangiocarcinoma are closely related to the dysregulation of transcription factors which promote cell proliferation, invasion, migration, angiogenesis, and drug resistance through reprogrammed transcriptional networks. It is of great significance to further explore and summarize the role of transcription factors in cholangiocarcinoma.

Areas covered: This review summarizes the oncogenic or tumor suppressive roles of key transcription factors in regulating cholangiocarcinoma progression and the potential targeting strategies of transcription factors in cholangiocarcinoma.

Expert opinion: Cholangiocarcinoma is a type of cancer highly influenced by transcriptional regulation, specifically transcription factors and epigenetic regulatory factors. Targeting transcription factors could be a potential and important strategy that is likely to impact future cholangiocarcinoma treatment.

Keywords: Cholangiocarcinoma; drug target; epigenetics; gene mutation; molecular mechanisms; transcription factor.

Publication types

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

MeSH terms

  • Bile Duct Neoplasms* / drug therapy
  • Bile Duct Neoplasms* / genetics
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology
  • Cholangiocarcinoma* / drug therapy
  • Cholangiocarcinoma* / genetics
  • Humans
  • Liver Neoplasms* / pathology
  • Transcription Factors / genetics

Substances

  • Transcription Factors