title: Cancer Stem Cell Plasticity Drives Therapeutic Resistance.
abstract: 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.
authors.affiliation: Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA. mrd85@case.edu.
authors.forename: Mary R
authors.initials: MR
authors.lastname: Doherty
authors.affiliation: Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA. jxs1094@case.edu.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Smigiel
authors.affiliation: Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA. damian.junk@case.edu.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Junk
authors.affiliation: Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA. mark.w.jackson@case.edu.|Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA. mark.w.jackson@case.edu.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Jackson
keywords: cancer stem cells; cellular plasticity; cytokines; epithelial-mesenchymal; therapeutic resistance; tumor microenvironment