Targeting tumor phenotypic plasticity and metabolic remodeling in adaptive cross-drug tolerance.

ABSTRACT: Metastable phenotypic state transitions in cancer cells can lead to the development of transient adaptive resistance or tolerance to chemotherapy. Here, we report that the acquisition of a phenotype marked by increased abundance of CD44 (CD44Hi) by breast cancer cells as a tolerance response to routinely used cytotoxic drugs, such as taxanes, activated a metabolic switch that conferred tolerance against unrelated standard-of-care chemotherapeutic agents, such as anthracyclines. We characterized the sequence of molecular events that connected the induced CD44Hi phenotype to increased activity of both the glycolytic and oxidative pathways and glucose flux through the pentose phosphate pathway (PPP). When given in a specific order, a combination of taxanes, anthracyclines, and inhibitors of g

SUBMITTER: Goldman A 

PROVIDER: S-EPMC7261372 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature