Ontology highlight
ABSTRACT:
SUBMITTER: Goel S
PROVIDER: S-EPMC4794996 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
Goel Shom S Wang Qi Q Watt April C AC Tolaney Sara M SM Dillon Deborah A DA Li Wei W Ramm Susanne S Palmer Adam C AC Yuzugullu Haluk H Varadan Vinay V Tuck David D Harris Lyndsay N LN Wong Kwok-Kin KK Liu X Shirley XS Sicinski Piotr P Winer Eric P EP Krop Ian E IE Zhao Jean J JJ
Cancer cell 20160301 3
Using transgenic mouse models, cell line-based functional studies, and clinical specimens, we show that cyclin D1/CDK4 mediate resistance to targeted therapy for HER2-positive breast cancer. This is overcome using CDK4/6 inhibitors. Inhibition of CDK4/6 not only suppresses Rb phosphorylation, but also reduces TSC2 phosphorylation and thus partially attenuates mTORC1 activity. This relieves feedback inhibition of upstream EGFR family kinases, resensitizing tumors to EGFR/HER2 blockade. Consequent ...[more]