NOXA Loss as a Major Mechanism of Intrinsic Resistance to Targeted Therapies in Breast Cancer
Abstract
Our grant hypothesis was that MCL-1 inhibition can sensitize HER2 inhibitors in HER2 amplified breast cancer and ER inhibitors in ER-positive breast cancer. We have provided preclinical evidence to support the use to ER inhibitors in combination with MCL-1 inhibitors in ER+ breast cancer and our findings have uncovered a novel axis of miRNA4728-NOXAMCL-1 as a key determinant of sensitivity of HER2 inhibitors in HER2 amplified breast cancers and ER inhibitors in ER+ breast cancers. In addition, HER2 inhibitor treatment and ER inhibitor treatment both lead to loss of NOXA, which causes a MCL-1addiction. in this sensitivity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2023
- Accession Number
- AD1210242
Entities
People
- Anthony Faber
- Jorge S Reis-Filho
Organizations
- Virginia Commonwealth University