Cancer Stem Cell Plasticity Drives Therapeutic Resistance

Cancers

Mary R. Doherty¹  Jacob M. Smigiel¹  Damian J. Junk¹  Mark W. Jackson¹  Zhe-Sheng (Jason) Chen² 

[1] Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA;;Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA

关键词: cancer stem cells;    therapeutic resistance;    cellular plasticity;    epithelial-mesenchymal;    tumor microenvironment;    cytokines;   

DOI  :  10.3390/cancers8010008

来源: mdpi

【 摘 要 】

The connection between epithelial-mesenchymal (E-M) plasticity and cancer stem cell (CSC) properties has been paradigm-shifting, linking tumor cell invasion and metastasis with therapeutic recurrence. However, despite their importance, the molecular pathways involved in generating invasive, metastatic, and therapy-resistant CSCs remain poorly understood. The enrichment of cells with a mesenchymal/CSC phenotype following therapy has been interpreted in two different ways. The original interpretation posited that therapy kills non-CSCs while sparing pre-existing CSCs. However, evidence is emerging that suggests non-CSCs can be induced into a transient, drug-tolerant, CSC-like state by chemotherapy. The ability to transition between distinct cell states may be as critical for the survival of tumor cells following therapy as it is for metastatic progression. Therefore, inhibition of the pathways that promote E-M and CSC plasticity may suppress tumor recurrence following chemotherapy. Here, we review the emerging appreciation for how plasticity confers therapeutic resistance and tumor recurrence.

【 授权许可】

CC BY   
© 2016 by the authors; licensee MDPI, Basel, Switzerland.