Insights into new mechanisms and models of cancer stem cell multidrug resistance

Seminars in Cancer Biology
Y Garcia-MayeaM E LLeonart

Abstract

The acquisition of genetic alterations, clonal evolution, and the tumor microenvironment promote cancer progression, metastasis and therapy resistance. These events correspond to the establishment of the great phenotypic heterogeneity and plasticity of cancer cells that contribute to tumor progression and resistant disease. Targeting resistant cancers is a major challenge in oncology; however, the underlying processes are not yet fully understood. Even though current treatments can reduce tumor size and increase life expectancy, relapse and multidrug resistance (MDR) ultimately remain the second cause of death in developed countries. Recent evidence points toward stem-like phenotypes in cancer cells, promoted by cancer stem cells (CSCs), as the main culprit of cancer relapse, resistance (radiotherapy, hormone therapy, and/or chemotherapy) and metastasis. Many mechanisms have been proposed for CSC resistance, such as drug efflux through ABC transporters, overactivation of the DNA damage response (DDR), apoptosis evasion, prosurvival pathways activation, cell cycle promotion and/or cell metabolic alterations. Nonetheless, targeted therapy toward these specific CSC mechanisms is only partially effective to prevent or abolish resis...Continue Reading

Citations

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