Molecular Targets in Precision Chemoprevention of Colorectal Cancer : An Update from Pre-Clinical to Clinical Trials

Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. The initiation and progression of CRC is a multi-step process that proceeds via precursor lesions to carcinoma, with each stage characterized by its distinct molecular and tissue microenvironment changes. Precursor lesions of CRC, aberrant crypt foci, and adenoma exhibit drastic changes in genetic, transcriptomic, and proteomic profiles compared to normal tissue. The identification of these changes is essential and provides further validation as an initiator or promoter of CRC and, more so, as lesion-specific druggable molecular targets for the precision chemoprevention of CRC. Mutated/dysregulated signaling (adenomatous polyposis coli, β-catenin, epidermal growth factor receptor, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), tumor protein53, Akt, etc.), inflammatory (cyclooxygenase-2, microsomal prostaglandin E synthase-1, inducible nitric oxide synthase, and other pro-inflammatory mediators), and metabolic/growth factor (fatty acid synthase, β-Hydroxy β-methylglutaryl-CoA reductase, and ornithine decarboxylase) related targets are some of the well-characterized molecular targets in the precision chemoprevention of CRC. In this review, we discuss precursor-lesion specific targets of CRC and the current status of pre-clinical studies regarding clinical interventions and combinations for better efficacy and safety toward future precision clinical chemoprevention. In addition, we provide a brief discussion on the usefulness of secondary precision chemopreventive targets for tertiary precision chemoprevention to improve the disease-free and overall survival of advanced stage CRC patients.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:21

Enthalten in:

International journal of molecular sciences - 21(2020), 24 vom: 17. Dez.

Sprache:

Englisch

Beteiligte Personen:

Yarla, Nagendra S [VerfasserIn]
Madka, Venkateshwar [VerfasserIn]
Pathuri, Gopal [VerfasserIn]
Rao, Chinthalapally V [VerfasserIn]

Links:

Volltext

Themen:

Adenomatous Polyposis Coli Protein
Antineoplastic Agents
Biomarkers
Biomarkers, Tumor
Colorectal cancer
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
EC 1.14.99.1
EC 2.3.1.85
Fatty Acid Synthases
Journal Article
Molecular targets
Precision prevention
Review

Anmerkungen:

Date Completed 15.03.2021

Date Revised 15.03.2021

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms21249609

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM319132013