Scientists Uncover Molecular Pathway that Makes Tumors More Aggressive

Researchers at the Moores Cancer Center at the University of California, San Diego discovered a molecular pathway that accounts for increased malignancy of various solid tumors. They believe that this molecular signature may also predict the likelihood of successful treatment with dasatinib, which is marketed as Sprycel by Bristol-Myers Squibb for the treatment of chronic myelogenous leukemia (CML).

The study was published September 6 in the advance online edition of Nature Medicine. The findings have reportedly led to discussions about the potential design of a clinical trial.

The researchers compared the growth properties of pancreatic and breast cancer cells that expressed the alpha-v beta-3 receptor versus those that did not. It led to the finding that this receptor activates an enzyme called src-kinase, which helps tumor cells become more aggressive in the body.

Dasatinib works by blocking this enzyme. “Once we identified the pathway, we immediately realized that the drug dasatinib, which targets this pathway, would be a logical choice to use against these cancers,” says David Cheresh, Ph.D., professor and vice chair of pathology.

The group's studies in a preclinical model of pancreatic cancer confirmed that those tumor cells with the receptor responded to the drug, while those not expressing receptors did not. The scientists thus think that the presence of the integrin alpha-v beta-3 receptor on some of the more common solid tumors such as breast, colon, lung, and pancreas could help identify individuals who are likely to respond to the drug. Dr. Cheresh points to pancreatic cancer tumors, approximately 60% of which carry the marker on the tumor cell surface.