Proposed mechanism. A Doxorubicin (DOX) targets the BCAA catabolic pathway in TNBCs, by downregulating BCKDK and augmenting clearance of intracellular BCKAs. B Genetic or pharmacological (high BT2 concentration) inhibition of BCKDK results in increased cell death, decreased intracellular BCKAs, dysregulated mitochondrial function, ATP insufficiency, SESN2 activation, and inhibition of mTORC1 signaling and protein synthesis. C BCKDK inhibition (siRNA mediated or low-BT2 concentration) exacerbates DOX-induced cytotoxicity and caspase activity.
- Dipsikha Biswas
- Logan Slade
- Thomas Pulinilkunnil
