Guanylyl cyclase C as a diagnostic and therapeutic target in colorectal cancer

Per Med. 2022 Sep;19(5):457-472. doi: 10.2217/pme-2022-0026. Epub 2022 Aug 3.

Abstract

Colorectal cancer remains a major cause of mortality in the USA, despite advances in prevention and screening. Existing therapies focus primarily on generic treatment such as surgical intervention and chemotherapy, depending on disease severity. As personalized medicine and targeted molecular oncology continue to develop as promising treatment avenues, there has emerged a need for effective targets and biomarkers of colorectal cancer. The transmembrane receptor guanylyl cyclase C (GUCY2C) regulates intestinal homeostasis and has emerged as a tumor suppressor. Further, it is universally expressed in advanced metastatic colorectal tumors, as well as other cancer types that arise through intestinal metaplasia. In this context, GUCY2C satisfies many characteristics of a compelling target and biomarker for gastrointestinal malignancies.

Keywords: GUCY2C; biomarker; cancer prevention; colorectal cancer; guanylin; guanylyl cyclase C; hormone replacement; linaclotide; plecanatide; uroguanylin.

Plain language summary

Colorectal cancer is a leading cause of death in the USA. In recent years, there has been a shift in the field of oncology from generic treatments, such as surgery and chemotherapy, to personalized molecular therapies, which focus on targeting specific attributes of each patient's unique cancer. Guanylyl cyclase C is a receptor expressed in the intestinal tract, where it regulates fluid secretion and prevents tumor formation. Beyond its function in the healthy intestine, it is expressed in colorectal tumors, and other types of cancer, where it regulates transformation. Therefore, guanylyl cyclase C can serve as a useful target in cancer for prevention and therapy, as well as a marker for tumor cell detection.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Colorectal Neoplasms* / diagnosis
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Humans
  • Receptors, Enterotoxin

Substances

  • GUCY2C protein, human
  • Receptors, Enterotoxin