Drug response marker may speed lung cancer prevention trials

Changes in the expression of microRNA-34c 6 months after treatment with a medicine to prevent lung cancer correlated with a benefit from the drug that was seen much later.

Currently, testing medicines to prevent lung cancer requires treating many thousands of high-risk persons and then waiting 5, 10, or 15 years to see which of them develop cancer and which, if any, derive a survival benefit from the treatment. This new study proposes a possible waypoint towards a benefit. If microRNA-34c is validated, the number of patients needed and time required to test drugs for lung cancer prevention could be dramatically reduced.

“Chemoprevention is an important approach that has been way behind in terms of scientific advances for lung cancer,” said Fred R. Hirsch, MD, PhD, investigator at the University of Colorado Cancer Center and professor of medical oncology and pathology at the CU School of Medicine. “If we could find a surrogate end point for lung cancer mortality—an intermediate end point—it would make it much easier to conduct smaller trials in much shorter time.”

Among persons who later showed a benefit from chemoprevention, microRNA-34c expression was down 6 months after treatment. In patients who showed no benefit, microRNA-34c expression remained unchanged.

“Instead of waiting for an end point 15 years in the future, we could potentially discover the effectiveness of chemopreventive agents only 6 months after treatment. It would speed up the pace of discovery and eventually bring new chemopreventive agents much faster to the market,” Hirsch said.

Hirsch cautioned that this discovery has potential, but further work is needed to validate the predictive power of microRNA-34c in showing chemopreventive response. However, microRNA-34c could be this predictive waypoint, and the cutting-edge technique of looking beneath genes, beneath even RNA and mRNA into the molecular world of microRNA may help in discovering the roots of the disease.

This study was published in Cancer Prevention Research (2012; doi:10.1158/1940-6207.CAPR-12-0382).

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