Summary
Research into targeted degradation of CDK4 and 6 to overcome treatment resistance in Estrogen Receptor-positive (ER+) breast cancer, focusing on the kinase-independent functions of CDK6.
Targeted degradation of CDK4 and 6 to overcome treatment resistance in breast cancer
US · IL
National Institutes of Health (NIH)
grant
open
#nih-1R01CA292377-01A1
What they want
The project aims to define the roles of kinase and non-kinase functions of CDK6 in conferring palbociclib resistance in CDK6-high, palbociclib-resistant cell line- and patient-derived xenograft (PDX) models of ER+ breast cancer using advanced 3D genomic and machine learning approaches. It will also evaluate the in vivo efficacy of a CDK4/6-selective degrader (CDK4/6-D) in these models, both as a single agent and in combination with endocrine therapy and checkpoint inhibition, including in a unique NeoThy humanized mouse model.
Technical requirements
- advanced 3D genomic approaches
- machine learning approaches
- CDK4/6-selective proteolysis targeting chimera (PROTAC)
- NeoThy humanized mouse model
