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Current Colorectal Cancer Reports

, Volume 13, Issue 3, pp 192–204 | Cite as

Chemoprevention of Colorectal Cancer in High-Risk Patients: from Molecular Targets to Clinical Trials

  • Dora Colussi
  • Franco Bazzoli
  • Luigi Ricciardiello
Basic Science Foundations in Colorectal Cancer (J Roper, Section Editor)
  • 105 Downloads
Part of the following topical collections:
  1. Topical Collection on Basic Science Foundations in Colorectal Cancer

Abstract

An increased understanding of the molecular pathways involved in colorectal carcinogenesis has helped researchers to develop possible chemopreventive strategies. This has been of particular relevance for high-risk subjects, for whom chemopreventive strategies may be helpful in slowing cancer development. In order to obtain more definitive data on chemopreventive agents, there has been a great effort to develop preclinical models that resemble the clinical scenarios encountered in high-risk patients. Importantly, many compounds, in particular non-steroidal anti-inflammatory drugs, have shown significant effects in models of high-risk clinical settings. However, results from clinical trials have been somewhat disappointing and no definitive chemopreventative agent is currently given for any of the high-risk conditions. In this review, we examine the available data on the effects of chemopreventive drugs on molecular targets relevant for high-risk conditions predisposing to colorectal cancer, including data from preclinical studies that have led to clinical trials.

Keywords

Chemoprevention Colorectal cancer Familial adenomatous polyposis Lynch syndrome Colitis associated colorectal cancer Aspirin Mesalamine Ecosapentainoic acid Ursodexycolic acid 

Abbreviations

CRC

Colorectal cancer

FAP

Familial adenomatous polyposis

APC

Adenomatous polyposis coli

AFAP

Attenuated familial adenomatous polyposis

NSAIDs

Non-steroidal anti-inflammatory drugs

PGs

Prostaglandins

PGE2

Prostaglandin E2

PGE3

Prostaglandin E3

COX-1

Cyclooxygenase-1

COX-2

Cyclooxygenase-2

PPARD

Peroxisome proliferator activated receptor delta

RXR-alpha

Retinoid X receptor alpha

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

ODC

Ornithine decarboxylase

DFMO

Difluoromethylornithine

P-S

Phosphosulindac

EGFR

Epidermal growth factor receptor

EP2-receptor

Prostaglandin E2 receptor

PI3K

Phosphoinositide 3-kinase

AKT

Protein kinase B

GSK3B

Glycogen synthase kinase 3 beta

PP2A

Protein phosphatase 2A

NO-ASA

Aspirin with a covalently attached NO-releasing moiety

CAPP-1

Colorectal adenoma/carcinoma prevention program 1

CAPP-2

Colorectal adenoma/carcinoma prevention program 2

TNF-a

Tumor necrosis factor-alpha

IFN-Y

Interferon gamma

Hif-1a

Hypoxia-inducible factor 1-alpha

VEGF

Vascular endothelial growth factor

DFMO

Difluoromethylornithine

EPA

Eicosapentaenoic acid

DHA

Docosahexaenoic acid

EPA-FFA

Eicosapentaenoic acid as free fatty acid

ω-3 PUFAs

Omega-3 polyunsaturated fatty acids

Rs

Resolvins

DIM

3,3′-diindolylmethane

IRA

Ileorectal anastomosis

IPAA

Ileal pouch-anal anastomosis

LS

Lynch syndrome

MMR

Mismatch repair

MLH1

MutL homolog 1

MSH2

MutS protein homolog 2

MSH6

MutS protein homolog 6

PMS2

Mismatch repair endonuclease 2

HCT116

Human colon cancer cells

MSI

Microsatellite instability

MSI-H

Microsatellite instability high

MSI-L

Microsatellite instability-low

TGFBR2

Transforming growth factor beta receptor II

ACVR2

Activin type 2 receptors

IBD

Inflammatory bowel disease

PCS

Primary sclerosing cholangitis

UC

Ulcerative colitis

CD

Crohn’s disease

CAC

Colitis-associated colorectal cancer

NOS-2

Nitric oxide synthase 2

IL-6

Interleukin-6

STAT-3

Signal transducer and activator of transcription 3

AOM

Modeling colitis-associated cancer with azoxymethane

DSS

Murine colitis modeling using dextran sulfate sodium

Notch1

Notch homolog 1, translocation-associated (Drosophila)

IL-1 beta

Interleukin 1 beta

PPAR-gamma

peroxisome proliferator-activated receptor gamma

5-ASA

5-Amino salicylate acid

AZA

Azathioprine

6-MP

6-Marcaptopurine

IL-10

Interleukin-10

SOCS3

Suppressor of cytokine signaling 3

UDCA

Ursodexycolic acid

ERK1

Extracellular signal-regulated kinases 1

ERK2

Extracellular signal-regulated kinases 2

EGF

Epidermal growth factor

IGF-1

Insulin growth factor-1

MAPK

Mitogen-activated protein kinases

cAMP

Cyclic AMP pathway

Notes

Acknowledgments

L.R. is supported by the Italian Association for Cancer Research (AIRC) IG Investigator Grant N. 14281 and the European Community’s Seventh Framework Program FP7/2007–2013 under grant agreement 311876, Pathway-27.

Compliance with Ethical Standards

Conflict of Interest

Dora Colussi declares that she has no conflict of interest.

Franco Bazzoli declares that he has no conflict of interest.

Luigi Ricciardiello has received research funding through grants from Takeda and SLA Pharma, and has received compensation from Tillotts Pharma AG for service as a consultant.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Dora Colussi
    • 1
  • Franco Bazzoli
    • 1
  • Luigi Ricciardiello
    • 1
  1. 1.Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly

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