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Review
. 2019 Jun 6:10:588.
doi: 10.3389/fphar.2019.00588. eCollection 2019.

Drugs Targeting Epigenetic Modifications and Plausible Therapeutic Strategies Against Colorectal Cancer

Srinivas Patnaik  1 , Anupriya  1
Affiliations
Review

Drugs Targeting Epigenetic Modifications and Plausible Therapeutic Strategies Against Colorectal Cancer

Srinivas Patnaik et al. Front Pharmacol. .

Abstract

Genetic variations along with epigenetic modifications of DNA are involved in colorectal cancer (CRC) development and progression. CRC is the fourth leading cause of cancer-related deaths worldwide. Initiation and progression of CRC is the cumulation of a variety of genetic and epigenetic changes in colonic epithelial cells. Colorectal carcinogenesis is associated with epigenetic aberrations including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs. Recently, epigenetic modifications have been identified like association of hypermethylated gene Claudin11 (CLDN11) with metastasis and prognosis of poor survival of CRC. DNA methylation of genes CMTM3, SSTR2, MDF1, NDRG4 and TGFB2 are potential epigenetic biomarkers for the early detection of CRC. Tumor suppressor candidate 3 (TUSC3) mRNA expression is silenced by promoter methylation, which promotes epidermal growth factor receptor (EGFR) signaling and rescues the CRC cells from apoptosis and hence leading to poor survival rate. Previous scientific evidences strongly suggest epigenetic modifications that contribute to anticancer drug resistance. Recent research studies emphasize development of drugs targeting histone deacetylases (HDACs) and DNA methyltransferase inhibitors as an emerging anticancer strategy. This review covers potential epigenetic modification targeting chemotherapeutic drugs and probable implementation for the treatment of CRC, which offers a strong rationale to explore therapeutic strategies and provides a basis to develop potent antitumor drugs.

Keywords: colorectal cancer; drugs; epigenetics; histone; therapy.

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Figures

Figure 1
Figure 1
Depiction of molecular mechanism of HDAC inhibitors as anticancer agents.
Figure 2
Figure 2
Depiction of mechanism of DNMT/HMT inhibitors as anticancer agents.
Figure 3
Figure 3
Overall mechanism of function of DNA methyltransferase inhibitors and HDAC inhibitors.
See this image and copyright information in PMC

References

    1. Alumkal J. J., Slottke R., Schwartzman J., Cherala G., Munar M., Graff J. N., et al. (2015). A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer. Invest. New Drugs 33 (2), 480–489. 10.1007/s10637-014-0189-z - DOI - PMC - PubMed
    1. Armaghany T., Wilson J. D., Chu Q., Mills G. (2012). Genetic alterations in colorectal cancer. Gastrointest. Cancer Res. 5 (1), 19. - PMC - PubMed
    1. Arnold M., Sierra M. S., Laversanne M., Soerjomataram I., Jemal A., Bray F. (2017). Global patterns and trends in colorectal cancer incidence and mortality. Gut 66 (4), 683–691. 10.1136/gutjnl-2015-310912 - DOI - PubMed
    1. Atadja P. (2009). Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges. Cancer Lett. 280 (2), 233–241. 10.1016/j.canlet.2009.02.019 - DOI - PubMed
    1. Bae J. S., Han M., Yao C., Chung J. H. (2016). Chaetocin inhibits IBMX-induced melanogenesis in B16F10 mouse melanoma cells through activation of ERK. Chem. Biol. Interact 245, 66–71. 10.1016/j.cbi.2015.12.021 - DOI - PubMed