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The HSP-RTK-Akt axis mediates acquired resistance to Ganetespib in HER2-positive breast cancer by Eyermann, Christopher E. (author);Haley, John D. (author);Alexandrova, Evguenia M. (author) is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is The HSP-RTK-Akt axis mediates acquired resistance to Ganetespib in HER2-positive breast cancer about?
## 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 temporarily, suppresses HER2-positive breast cancer in genetic mouse models, but the animals eventually succumb via acquired resistance. We found that Ganetespib-resistant tumors upregulate several compensatory HSPs, as well as a wide network of phospho-activated receptor tyrosine kinases (RTKs), many of which are HSP clients. Downstream of p-RTKs, the MAPK pathway remains suppressed i
Who reads The HSP-RTK-Akt axis mediates acquired resistance to Ganetespib in HER2-positive breast cancer?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Eyermann, Christopher E. (author);Haley, John D. (author);Alexandrova, Evguenia M. (author)
- Publisher
- Springer Science and Business Media LLC
- Published
- 2021
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)