The HSP-RTK-Akt axis mediates acquired resistance to Ganetespib in HER2-positive breast cancer.

ABSTRACT: Breast cancer is the leading cause of cancer-related death in women worldwide. Human epidermal growth factor receptor 2 (HER2)-positive subtype comprises 20% of sporadic breast cancers and is an aggressive disease. While targeted therapies have greatly improved its management, primary and acquired resistance remain a major roadblock to making it a curable malignancy. Ganetespib, an Hsp90 (Heat shock protein 90) small molecule inhibitor, shows preferential efficacy in HER2-positive breast cancer, including therapy-refractory cases, and has an excellent safety profile in ongoing clinical trials (38 in total, six on breast cancer). However, Ganetespib itself evokes acquired resistance, which is a significant obstacle to its clinical advancement. Here, we show that Ganetespib potently, albeit

SUBMITTER: Eyermann CE 

PROVIDER: S-EPMC7838268 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature