A molecular signature that helps account for the aggressive behavior of a variety of cancers such as pancreatic, breast and melanoma may also predict the likelihood of successful treatment with a particular anti-cancer drug. The finding, which could lead to a personalized approach to treatment for a variety of solid tumors that are currently resistant to therapies, will be published September 6 in the advance online edition of Nature Medicine.
Researchers at the Moores Cancer Center at the University of California, San Diego have discovered that a receptor sitting on the surface of certain aggressive tumor cells can activate a key enzyme, src-kinase, which helps tumor cells become more aggressive in the body. This enzyme is the target of the anticancer drug dasatinib, which blocks its activity and is currently approved for treating chronic myelogenous leukemia (CML). The scientists say that the presence of the receptor - a protein called integrin alpha-v beta-3 - on some of the more common solid tumors such as breast, colon, lung and pancreas could help identify individuals with many other types of cancer that are also likely to respond to the drug.
"These results could enable us to identify the subpopulation of cancer patients who are likely to respond to treatment with dasatinib," said David Cheresh, PhD, professor and vice chair of pathology at the UC San Diego School of Medicine and the Moores UCSD Cancer Center, who led the work. "Rather than treat all patients with a given tumor type the same way, by identifying a specific molecular signature consisting of the receptor and its activated enzyme, we can customize the treatment in such a way that we impact the patients most likely to be sensitive to a drug."
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, which led to the discovery of a molecular pathway that accounted for the increased malignancy.