EMT, CTCs and CSCs in tumor relapse and drug-resistance

Abhisek Mitra, Lopa Mishra and Shulin Li _

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Oncotarget. 2015; 6:10697-10711. https://doi.org/10.18632/oncotarget.4037

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Abhisek Mitra1, Lopa Mishra2 and Shulin Li1

1 Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2 Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence to:

Shulin Li, email:

Keywords: tumor relapse, CTCs, CSCs, EMT, clinical trials

Received: February 02, 2015 Accepted: April 20, 2015 Published: May 08, 2015


Tumor relapse and metastasis are the primary causes of poor survival rates in patients with advanced cancer despite successful resection or chemotherapeutic treatment. A primary cause of relapse and metastasis is the persistence of cancer stem cells (CSCs), which are highly resistant to chemotherapy. Although highly efficacious drugs suppressing several subpopulations of CSCs in various tissue-specific cancers are available, recurrence is still common in patients. To find more suitable therapy for relapse, the mechanisms underlying metastasis and drug-resistance associated with relapse-initiating CSCs need to be identified. Recent studies in circulating tumor cells (CTCs) of some cancer patients manifest phenotypes of both CSCs and epithelial-mesenchymal transition (EMT). These patients are unresponsive to standard chemotherapies and have low progression free survival, suggesting that EMT-positive CTCs are related to co-occur with or transform into relapse-initiating CSCs. Furthermore, EMT programming in cancer cells enables in the remodeling of extracellular matrix to break the dormancy of relapse-initiating CSCs. In this review, we extensively discuss the association of the EMT program with CTCs and CSCs to characterize a subpopulation of patients prone to relapses. Identifying the mechanisms by which EMT-transformed CTCs and CSCs initiate relapse could facilitate the development of new or enhanced personalized therapeutic regimens.

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