Nat Commun:EZH2-mediated PP2A infraste-mediated resistance to HER2 targeted therapy for breast cancer

Her2 targeted therapy can significantly improve the prognostics of HER2-positive breast cancer patients.
, nearly half of these patients suffer from relapses due to inherent or accessive resistance.
, it is urgent to develop other targeted treatment strategies to overcome resistance to clinical treatment.
the study revealed that PP2A (protein phosphatase 2A) regulation of sub-base PPP2R2B is a key determinant of anti-HER2 reaction.
researchers found that expression levels of PPP2R2B were lower in HER2 plus breast cancer patients, which was associated with poor clinical outcomes and resistance to HER2 targeted therapies.
PPP2R2B expression reduction increased the risk of disease occurrence and HER2 targeted treatment adverse reactions researchers found that EZH2-mediated histoprotein modification can cause PPP2R2B expression reduction, resulting in PPP2A target p70S6K and 4EBP1 continuous phosphorylation, and thus mediate the inhibition of HER2 targeted therapy.
Genetic knock-off or inhibition of EZH2 by EZH2 inhibitors restores the expression of PPP2R2B, removes residual phosphorylation of p70S6K and 4EBP1, and makes HER2 plus breast cancer cells resensitive to HER2 targeted therapy.
addition, the same pharmacogenetic mechanisms contribute to the development of access resistance.
PPP2R2B's role model in HER2 targeted therapy sensitivity, these results show that the PPP2R2B inhibition of EZH2 dependence is an express genetic regulation of HER2 targeted therapy resistance, and EZH2 inhibitors also provide potential possibilities to reduce HER2 target therapy resistance.
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