mTOR-driven autophagy suppression defines metabolic vulnerability in CDK4/6 inhibitor-resistant HR+/HER2- breast cancer - PubMed
a day ago
- #breast cancer
- #metabolic vulnerability
- #CDK4/6 inhibitors
- mTOR-driven autophagy suppression creates a metabolic vulnerability in CDK4/6 inhibitor-resistant HR+/HER2- breast cancer.
- CDK4/6 inhibitors combined with endocrine therapy are a standard treatment for metastatic HR+/HER2- breast cancer, but resistance remains a challenge.
- Resistant clones show mTORC1 hyperactivation and autophagy suppression, leading to sensitivity to metabolic inhibitors like Metformin and Dichloroacetate (DCA).
- mTORC1 overactivation impairs autophagy via ULK1-Ser757 phosphorylation, making resistant cells unable to adapt to energy stress.
- Clinical data supports the correlation between mTORC1 activity and autophagy suppression, suggesting potential biomarkers for metabolic vulnerability.
- Targeting mTORC1-mediated autophagy defects with metabolic therapies could help overcome resistance in CDK4/6 inhibitor-resistant breast cancer.