Clinical implications of colorectal cancer stem cells in the age of single-cell omics and targeted therapies

Document Type

Journal Article

Publication Title

Gastroenterology

Volume

160

Issue

6

First Page

1947

Last Page

1960

PubMed ID

33617889

Publisher

Elsevier

School

School of Medical and Health Sciences

RAS ID

38829

Funders

Veterans Affairs Biomedical Laboratory Research and Development Veterans Affairs Rehabilitation Research and Development Department of Defense Translational Team Science Award National Institutes of Health/National Cancer Institute

Comments

Frank, M. H., Wilson, B. J., Gold, J. S., & Frank, N. Y. (2021). Clinical implications of colorectal cancer stem cells in the age of single-cell OMICs and targeted therapies. Gastroenterology, 160(6), 1947-1960. https://doi.org/10.1053/j.gastro.2020.12.080

Abstract

The cancer stem cell (CSC) concept emerged from the recognition of inherent tumor heterogeneity and suggests that within a given tumor, in analogy to normal tissues, there exists a cellular hierarchy composed of a minority of more primitive cells with enhanced longevity (ie, CSCs) that give rise to shorter-lived, more differentiated cells (ie, cancer bulk populations), which on their own are not capable of tumor perpetuation. CSCs can be responsible for cancer therapeutic resistance to conventional, targeted, and immunotherapeutic treatment modalities, and for cancer progression through CSC-intrinsic molecular mechanisms. The existence of CSCs in colorectal cancer (CRC) was first established through demonstration of enhanced clonogenicity and tumor-forming capacity of this cell subset in human-to-mouse tumor xenotransplantation experiments and subsequently confirmed through lineage-tracing studies in mice. Surface markers for CRC CSC identification and their prospective isolation are now established. Therefore, the application of single-cell omics technologies to CSC characterization, including whole-genome sequencing, RNA sequencing, and epigenetic analyses, opens unprecedented opportunities to discover novel targetable molecular pathways and hence to develop novel strategies for CRC eradication. We review recent advances in this field and discuss the potential implications of next-generation CSC analyses for currently approved and experimental targeted CRC therapies.

DOI

10.1053/j.gastro.2020.12.080

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