New breast cancer driver
August 26, 2016 | Leigh MacMillan
Approximately 20 percent of breast cancers have overexpression of the protein HER2, which drives signaling by the protein kinase Akt and is a marker of aggressive disease. The protein complex Rictor/mTORC2 is a known activator of Akt, but its role in breast cancer formation, progression and treatment is unclear.
Rebecca Cook, Ph.D., and colleagues have now demonstrated a role for Rictor/mTORC2 in breast cancers overexpressing HER2.
The investigators demonstrated that Rictor was upregulated in invasive breast cancer samples and that genetic disruption of Rictor function in a mouse model of HER2-amplified breast cancer decreased cell survival and reduced tumor burden. They showed that an mTORC1/2 dual inhibitor reduced survival of HER2-amplified cancer cells, including cells that were resistant to the HER2-blocking drug lapatinib.
The findings, reported in the Aug. 15 issue of Cancer Research, establish that Rictor/mTORC2 drives tumor progression in HER2-amplified breast cancers. The results also support continued clinical investigation of dual mTORC1/2 inhibitors and development of mTORC2-specific therapeutics.
This research was supported by grants from the National Institutes of Health (CA143126, CA186329, TR000445, CA195989), the Department of Defense (W81XWH-12-1-0026) and Susan G. Komen for the Cure (KG100677).