August 26, 2016

New breast cancer driver

Vanderbilt investigators have demonstrated that a certain protein complex drives tumor progression in aggressive breast cancers.

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).

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