Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies

Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies

Volume 8 in Cancer Sensitizing Agents for Chemotherapy
2020, Pages 57-74
Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies

Chapter 3 - Role of colorectal cancer stem cells in resistance to apoptosis and treatment in colorectal cancer

https://doi.org/10.1016/B978-0-12-819937-4.00003-0Get rights and content

Abstract

Colorectal cancer (CRC) is one of the most common malignancies which expresses high mortality, rapid metastasis, and relapse leading to patient death. Substantial evidence has revealed that cancer stem cells (CSCs) play a central role in the metastasis and relapse of CRC and render CRC highly resistant to cancer chemotherapeutic agents, radiotherapy, and apoptosis. These cells are a rare subpopulation of cancer cells endowed with specific properties including self-renewal, unlimited cell division, and differentiation potential. CSCs are immunophenotypically identified using several cell surface markers including CD24, CD133, CD44, EpCAM, LGR5, and ALDH. Therapy and apoptosis resistance are mediated by increased drug efflux capacity, increased expression of Musashi homolog 1 (MSI1), upregulation of antiapoptotic proteins, expression of particular microRNAs, and the interaction between CSC and their niche or supporting microenvironment. Because CSCs are highly tumorigenic, chemo- and drug-resistant, they play a significant role in the metastasis and recurrence of CRC. This chapter focuses on colorectal CSCs with emphasis on their mechanisms of drug and apoptosis resistance and tumor recurrence.

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