February 20, 2017

Improving therapies for GI tumors

A signaling protein overexpressed in upper gastrointestinal cancers is an attractive therapeutic target.

The signaling protein Aurora kinase A (AURKA) is overexpressed in several cancer types and has diverse oncogenic functions, making it an attractive druggable cancer target. Wael El-Rifai, M.D., Ph.D., and colleagues are exploring a role for AURKA in upper gastrointestinal cancers, which are characterized by poor patient survival and resistance to chemotherapy.

Using in vitro and in vivo models of upper gastrointestinal cancers, the investigators found that AURKA activates EIF4E (protein translation initiation factor) and cap-dependent translation and increases levels of the cancer-associated factor c-MYC.

Targeting AURKA genetically or with the small molecule inhibitor alisertib reversed these molecular events, reduced cancer cell survival in vitro and induced in vivo tumor regression of upper gastrointestinal cancer models that are resistant to the mTOR inhibitor everolimus.

In their report in Clinical Cancer Research, the researchers propose targeting AURKA as a novel therapeutic strategy to treat tumors resistant to mTOR inhibitors and those that have activation of EIF4E and c-MYC.

This research was supported by a Research Career Scientist award from the U.S. Department of Veterans Affairs and by grants from the National Institutes of Health (CA131225, CA093999, CA095103, CA068485, DK058404).

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