Targeting the Mevalonate Pathway to Overcome Acquired Anti-HER2 Treatment Resistance in Breast Cancer.

ABSTRACT: Despite effective strategies, resistance in HER2⁺ breast cancer remains a challenge. While the mevalonate pathway (MVA) is suggested to promote cell growth and survival, including in HER2⁺ models, its potential role in resistance to HER2-targeted therapy is unknown. Parental HER2⁺ breast cancer cells and their lapatinib-resistant and lapatinib + trastuzumab-resistant derivatives were used for this study. MVA activity was found to be increased in lapatinib-resistant and lapatinib + trastuzumab-resistant cells. Specific blockade of this pathway with lipophilic but not hydrophilic statins and with the N-bisphosphonate zoledronic acid led to apoptosis and substantial growth inhibition of R cells. Inhibition was rescued by mevalonate or the intermediate metaboli

SUBMITTER: Sethunath V 

PROVIDER: S-EPMC6825570 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature