April 21, 2014
Researchers Discover Biomarker Leading To Cancer Drug Resistance
redOrbit staff & Wire Reports – Your Universe Online
Researchers from the University of California, San Diego School of Medicine have located a biomarker that they believe could help explain why many of the medications used to treat lung, breast and pancreatic cancers also promote drug resistance and ultimately cause tumors to form in patients.
Writing in the April 20 online edition of Nature Cell Biology, the study authors report the discovery of a molecule known as CD61 that is present on the surface of drug-resistant tumors and could be responsible for inducing tumor metastasis by enhancing cancer cells’ stem cell-like properties. The discovery could lead to the development of ways to reverse drug resistance in an array of different cancer types.
“There are a number of drugs that patients respond to during their initial cancer treatment, but relapse occurs when cancer cells become drug-resistant,” Dr. David Cheresh, Distinguished Professor of Pathology at the UCSD School of Medicine, said in a statement Sunday. “We looked at the cells before and after they became resistant and asked, 'What has changed in the cells?'”
Dr. Cheresh and his colleagues analyzed how tumor cells become resistant to receptor tyrosine kinase inhibitors such as erlotinib or lapatinib, which are frequently used in standard cancer treatment programs. They discovered that as the drug resistance occurs, the tumor cells acquire stem cell like properties that provide them with the ability to essentially ignore the drugs and remain alive throughout a person’s body.
In particular, the researchers said that they delineated the molecular pathway responsible for facilitating both drug resistance and cancer stemness. By doing so, they identified current medications that exploit the pathway, reversing the tumors’ stem cell like traits and making the cancer cells susceptible to the drugs they had once resisted.
On the heels of these findings, Dr. Hatim Husain, an assistant professor who also treats lung and brain cancer patients at Moores Cancer Center, has devised a clinical trial to attack this particular pathway in patients with drug-resistant tumors. The trial, which will be open to lung cancer patients who have become resistant to erlotinib, is expected to begin within the next 12 months.
“Resistance builds to targeted therapies against cancer, and we have furthered our understanding of the mechanisms by which that happens,” Husain said. “Based on these research findings we now better understand how to exploit the 'Achilles heel' of these drug-resistant tumors. Treatments will evolve into combinational therapies where one may keep the disease under control and delay resistance mechanisms from occurring for extended periods of time.”
While the trial will initially feature only patients who have already experienced drug resistance, Husain hopes to eventually expand it to include men and women in earlier stages in order to prevent initial resistance. The study, which was funded in part by grants from the National Institutes of Health and the National Cancer Institute, also involved experts from the University of Texas MD Anderson Cancer Center.