Intestine-specific FXR agonists as potential therapeutic agents for colorectal cancer

Biochem Pharmacol. 2021 Apr:186:114430. doi: 10.1016/j.bcp.2021.114430. Epub 2021 Feb 6.

Abstract

Colorectal cancer (CRC) is one of the most malignant cancers in the world. A major cause of death in CRC patients is the limited therapeutic options in its advanced stages. The Farnesoid X receptor (FXR) is a member of the nuclear superfamily, which is effective in slowing the progression of colorectal cancer in addition to its extraordinary role in regulating metabolic disorders. Due to the systemic side-effects caused by non-selective agonists, the intestine-restricted FXR agonists can induce a whole-body benefit without activating the hepatic FXR, suggesting intestinal FXR activation as a potentially safer therapy in the treatment of CRC. This review highlights the effects of FXR on the disturbed bile acid circulation and the carcinogenesis of CRC and with a specific emphasis on listing the functions of several intestinal-restricted FXR agonists.

Keywords: Colorectal cancer; Farnesoid X receptor; Intestine-restricted FXR agonists; Mechanism.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Azetidines / pharmacology
  • Azetidines / therapeutic use
  • Benzene Derivatives / pharmacology
  • Benzene Derivatives / therapeutic use
  • Bile Acids and Salts / metabolism
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Humans
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Isonicotinic Acids / pharmacology
  • Isonicotinic Acids / therapeutic use
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / metabolism

Substances

  • Antineoplastic Agents
  • Azetidines
  • Benzene Derivatives
  • Bile Acids and Salts
  • Isonicotinic Acids
  • Receptors, Cytoplasmic and Nuclear
  • fexaramine
  • farnesoid X-activated receptor
  • cilofexor