Creating a free account will enable you to subscribe to our daily and weekly email newsletters, as well as customize your reading experience to show only the categories most relevant to you.
Signing up only take a few minutes, so why not give it a try and see what you've been missing out on.
Johns Hopkins scientists have identified a molecular marker called "Mig 6" that appears to accurately predict longer survival - up to two years - among patients prescribed two of the most widely used drugs in a class of anticancer agents called EGFR inhibitors.
The U.S. Food and Drug Administration-approved drugs, gefitinib (Iressa) and erlotinib (Tarceva), are prescribed for lung and pancreatic cancer patients but only a few who have mutations in the EGFR gene usually benefit with a prolonged reduction of tumor size. The two drugs block the gene's ramped-up protein production, but patients' response to the drug varies widely - from no survival benefit to several years. The average is several months.
"Clinicians have had no reliable method for distinguishing patients who are not likely to respond to EGFR inhibitors and those who will respond very well," says David Sidransky, M.D., professor of otolaryngology, oncology, pathology, urology, and genetics at Johns Hopkins. Looking at the precise level of protein production from the EGFR gene alone in specific patients was not proven to be a good indicator of patients' response to EGFR-blocking drugs, but the presence or absence of Mig 6 might be, he adds.
In a preliminary study, described July 31 in the online journal, PLoS ONE, the Johns Hopkins scientists found the genetic marker in a series of experiments that began with laboratory-derived lung and head and neck cancer cell lines resistant to EGFR-inhibitor drugs. In the cell lines, the team found very high levels of protein production from the Mig 6 gene - up to three times the level in sensitive cell lines. Mig 6 is one of the molecules that controls the activity of the EGFR protein.
"In the first set of experiments, we found that higher levels of Mig 6 occur often in cells that don't respond to EGFR inhibitors," says Sidransky. "Most tumors are known to have high Mig 6 levels and are not expected to respond to EGFR inhibitors."
Next, the research team studied Mig 6 levels in a variety of tumors that were directly engrafted into mice, a research model known as a xenograft, and treated with an EGFR inhibitor. These new models contain a more complete sampling of the tumor that includes "stromal" cells, which surround and interact with the cancer cells. "These tumors are implanted along with their own microenvironment, into the mice, and we believe this model may be more predictive of what happens in human patients," says Sidransky.
In the xenografts of tumors without EGFR mutations, as Mig 6 levels increased, so did the resistance to EGFR inhibitors, suggesting a correlation between high Mig 6 and lack of response to the drugs. To confirm the correlation, the scientists tested tissue samples of 65 lung cancer patients treated with EGFR inhibitors to compare their Mig 6 levels with outcomes.
Of 18 patients with low Mig 6 levels, five of them survived more than a year without progression of their cancer; four survived more than two years progression-free. Among 16 patients with higher Mig 6 levels, two survived more than one year and none survived, progression-free, beyond two years.
"The beauty of this finding is that it's simple. We're looking for tumors with low levels of Mig 6 to predict clinical benefit, and there aren't many of them," says Sidransky.
Sidransky's team expects to license the Mig 6 marker to a biotechnology or pharmaceutical company and conduct further tests in larger groups of patients.
The research was funded by the National Institutes of Health (National Cancer Institute, P50 DE019032, U01 CA084986, and R37DE012588) and FAMRI (The Flight Attendant Medical Research Institute).
In addition to Sidransky, other scientists who contributed to the research include Xiaofei Chang, Aditi Chatterjee, Shizhang Ling, Constance L. Monitto, Myoung Sook Kim, David M. Berman, Steve Goodman, Ignacia I Wistuba, and Atul Bedi from Johns Hopkins; Luisa M Solis, Ignacia I Wistuba from the MD Anderson Cancer Center; Shyhmin Huang and Paul M. Harari from the University of Wisconsin; and Manuel Hidalgo from the Centro Intregral Oncologico Clara Campal, Madrid, Spain.
The Relative Expression of Mig6 and EGFR Is Associated with Resistance to EGFR Kinase Inhibitors, PLoS ONE 8(7): e68966. doi:10.1371/journal.pone.0068966
Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our Cancer / Oncology category page for the latest news on this subject.
Please use one of the following formats to cite this article in your essay, paper or report:
Medicine, Johns Hopkins. "Molecular marker predicts patients most likely to benefit longest from 2 popular cancer drugs." Medical News Today. MediLexicon, Intl., 9 Sep. 2013. Web.
9 Dec. 2013. <http://www.medicalnewstoday.com/releases/265754>
Medicine, J. (2013, September 9). "Molecular marker predicts patients most likely to benefit longest from 2 popular cancer drugs." Medical News Today. Retrieved from
Please note: If no author information is provided, the source is cited instead.
If you write about specific medications, operations, or procedures please do not name healthcare professionals by name.
For any corrections of factual information, or to contact the our editorial team, please use our feedback form. Please send any medical news or health news press releases to:
Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.
This page was printed from: http://www.medicalnewstoday.com/releases/265754.php
Visit www.medicalnewstoday.com for medical news and health news headlines posted throughout the day, every day.
© 2004-2013 All rights reserved. MNT (logo) is the registered trade mark of MediLexicon International Limited.