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. 2021;6(2):117-129.
doi: 10.1080/23808993.2021.1876518. Epub 2021 Feb 2.

GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer

Amanda N Lisby  1 , John C Flickinger Jr  1 , Babar Bashir  2 , Megan Weindorfer  1 , Sanjna Shelukar  1 , Madison Crutcher  3 , Adam E Snook  1 , Scott A Waldman  1
Affiliations

GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer

Amanda N Lisby et al. Expert Rev Precis Med Drug Dev. 2021.

Abstract

Introduction: Colorectal cancer (CRC) is one of the most-deadly malignancies worldwide. Current therapeutic regimens for CRC patients are relatively generic, based primarily on disease type and stage, with little variation. As the field of molecular oncology advances, so too must therapeutic management of CRC. Understanding molecular heterogeneity has led to a new-found promotion for precision therapy in CRC; underlining the diversity of molecularly targeted therapies based on individual tumor characteristics.

Areas covered: We review current approaches for the treatment of CRC and discuss the potential of precision therapy in advanced CRC. We highlight the utility of the intestinal protein guanylyl cyclase C (GUCY2C), as a multi-purpose biomarker and unique therapeutic target in CRC. Here, we summarize current GUCY2C-targeted approaches for treatment of CRC.

Expert opinion: The GUCY2C biomarker has multi-faceted utility in medicine. Developmental investment of GUCY2C as a diagnostic and therapeutic biomarker offers a variety of options taking the molecular characteristics of cancer into account. From GUCY2C-targeted therapies, namely cancer vaccines, CAR-T cells, and monoclonal antibodies, to GUCY2C agonists for chemoprevention in those who are at high risk for developing colorectal cancer, the utility of this protein provides many avenues for exploration with significance in the field of precision medicine.

Keywords: Antibody Therapy; Biomarker; CAR-T Cell Therapy; Cancer Vaccine; Colorectal Cancer; GUCY2C; Guanylyl Cyclase C.

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Conflict of interest statement

Declaration of interests SAW is the Chair of the Scientific Advisory Board and member of the Board of Directors of, and AES is a consultant for, Targeted Diagnostics & Therapeutics, Inc. which provided research funding that, in part, supported this work and has a license to commercialize inventions related to this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1:
Figure 1:. GUCY2C downstream signaling pathway.
In the presence of ligands, guanylin and uroguanylin, the GUCY2C receptor converts GTP into cGMP maintaining healthy mitochondrial function, genomic stability, and epithelial barrier integrity. In the absence of ligands, GUCY2C silencing causes downstream metabolic dysfunction, genomic instability, and barrier dysfunction; Created with BioRender.com
Figure 2:
Figure 2:. GUCY2C as a target for precision therapy in the treatment of colorectal cancer.
CAR – chimeric antigen receptor; ADC – Antibody Drug Conjugate; Created with BioRender.com
See this image and copyright information in PMC

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