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Precision Targeting of <i>pten</i>-Null Triple-Negative Breast Tumors Guided by Electrophilic Metabolite Sensing

Xuyu Liu, Marcus J. C. Long, Benjamin D. Hopkins, Chaosheng Luo, Lingxi Wang, Yimon Aye

2020ACS Central Science39 citationsDOIOpen Access PDF

Abstract

-null triple-negative breast cancers (TNBCs). MK-H(F)NE further enables novel downstream target identification specific to Akt3-function in disease. In TNBC xenografts, MK-H(F)NE fares better than reversible pan-Akt-inhibitors and does not show commonly observed side-effects associated with Akt1-inhibition. Inhibitors derived from native-metabolite sensing are thus an enabling plan-of-action for unmasking kinase-isoform-biased molecular targets and tumor-subtype-specific interventions.

Topics & Concepts

PTENAKT1MetaboliteCancer researchTriple-negative breast cancerGene isoformComputational biologyBiologyChemistryProtein kinase BPI3K/AKT/mTOR pathwayBiochemistryBreast cancerSignal transductionCancerGeneGeneticsPI3K/AKT/mTOR signaling in cancerProtein Degradation and InhibitorsCancer-related gene regulation
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