Synergistic Inhibition of Kinase Pathways Overcomes Resistance of Colorectal Cancer Spheroids to Cyclic Targeted Therapies.

ABSTRACT: Cancer cells often adapt to single-agent treatments with chemotherapeutics. Activation of alternative survival pathways is a major mechanism of drug resistance. A potential approach to block this feedback signaling is using combination treatments of a pair of drugs, although toxicity has been a limiting factor. Preclinical tumor models to identify mechanisms of drug resistance and determine low but effective combination doses are critical to effectively suppress tumor growth with reduced toxicity to patients. Using our aqueous two-phase system microtechnology, we developed colorectal tumor spheroids in high-throughput and evaluated resistance of cancer cells to three mitogen-activated protein kinase inhibitors (MAPKi) in long-term cyclic treatments. Our quantitative analysis showed that th

SUBMITTER: Thakuri PS 

PROVIDER: S-EPMC7088992 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature