JNK Pathway Activation Modulates Acquired Resistance to EGFR/HER2-Targeted Therapies.

ABSTRACT: Resistance limits the effectiveness of receptor tyrosine kinase (RTK)-targeted therapies. Combination therapies targeting resistance mechanisms can considerably improve response, but will require an improved understanding of when particular combinations will be effective. One common form of resistance is bypass signaling, wherein RTKs not targeted by an inhibitor can direct reactivation of pathways essential for survival. Although this mechanism of resistance is well appreciated, it is unclear which downstream signaling events are responsible. Here, we apply a combined experimental- and statistical modeling-based approach to identify a set of pathway reactivation essential for RTK-mediated bypass resistance. Differences in the downstream pathway activation provided by particular RTKs lead

SUBMITTER: Manole S 

PROVIDER: S-EPMC5026573 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature