August 25, 2020

Blocking tumor ‘signals’ and ‘fuel’

Combining two drugs reduced colorectal cancer cell growth in vitro and in an animal model, suggesting the combination may be a promising treatment for patients.

The EGFR-targeted therapies cetuximab and panitumumab are approved for patients with advanced colorectal cancer with wild-type RAS, but patients commonly acquire resistance. 

H. Charles Manning, PhD, and colleagues explored the idea of combining EGFR-targeted therapy with a drug (CB-839) that blocks cancer cell glutamine metabolism — to cut off both the “signals” and the “fuel” for tumor growth and proliferation. 

The researchers treated colorectal cancer cell lines with single or combination therapy and tested the effects in 2D and 3D in vitro assays. Led by Allison Cohen, PhD, the authors reported in Translational Oncology that the combination of cetuximab with CB-839 reduced cell viability and was synergistic in several cell lines. They also tested the treatment using xenograft animal models and found significant reduction in tumor growth and reduced markers of proliferation, along with increased cell death. 

The combination therapy was effective against cetuximab-sensitive and resistant cell lines, suggesting that it may be a promising therapy for patients with metastatic wild-type RAS colorectal cancer.

This research was supported by the National Institutes of Health (grants CA220325, CA236733, CA068485) and the Vanderbilt Center for Molecular Probes.