August 20, 2020

A “torque” for tumor blood vessels

Vanderbilt scientists have discovered a new target for normalizing tumor blood vessels to improve cancer immunotherapies.

Tumors tend to have leaky and highly dysfunctional blood vessels that can prevent anti-cancer drugs and immune cells from getting to them. Improving the effectiveness of cancer therapy, therefore, may require finding ways to “normalize” tumor blood vessels.  

Signaling through a protein complex called mTORC1 is thought to affect cellular proliferation in the vascular endothelial cells that line the interior of blood vessels.  

Reporting in the journal JCI InsightJin Chen, MD, PhD, and colleagues demonstrate that genetic deletion of a component of mTORC1 in mice caused tumor blood vessel normalization, an increase in tumor-infiltrating lymphocytes and decreased tumor growth. 

A low dose of RAD001, which inhibits mTORC1, also promoted tumor vessel normalization and increased tumor immunity. 

These findings suggest that endothelial mTORC1 inhibition is a novel approach to normalize tumor blood vessels and enhance cancer treatments and emerging immunotherapies. Because RAD001 is a clinically approved drug, these results can be quickly translated into clinical trials, the researchers concluded. 

This work was supported by National Institutes of Health grants CA117681, CA095004, GM000734 and CA216891, by a Veterans Affairs Merit Award and by a Veterans Affairs Research Career Scientist Award.