Navigation Links
Molecular marker predicts patients most likely to benefit longest from 2 popular cancer drugs
Date:9/5/2013

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.


'/>"/>

Contact: Vanessa Wasta
wastava@jhmi.edu
410-614-2916
Johns Hopkins Medicine
Source:Eurekalert

Related medicine news :

1. Molecular Imaging, Inc. Announces New Webinar: Advancing Discovery and Development of Biologics Through Non-Invasive Biodistribution Imaging
2. Janina A. Longtine, MD of the Icahn School of Medicine at Mount Sinai Elected President of the Association for Molecular Pathology
3. Dartmouth researchers develop molecular switch that changes liquid crystal colors
4. Mount Sinai and Exosome Partner to Accelerate Translation of Body Fluid Molecular Diagnostics to Overcome Limitations of Tissue Biopsy in Areas of Unmet Medical Needs
5. Molecular Diagnostics Market - New Industry Research Report is Now Available for Pre-Order at Transparency Market Research
6. New study shows vitamin D-related molecular switches predict childhood bone mass
7. EurekaMag.com Publishes 64 Thousand New Animal Science References and Bibliography on Molecular Cloning
8. Molecular switch controls the destiny of self-eating cells
9. The Association for Molecular Pathology announces 2013 Leadership Award recipient
10. Abnormalities in new molecular pathway may increase breast cancer risk
11. Researchers gain new molecular-level understanding of the brains recovery after stroke
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/26/2016)... ... ... Connor Sports, through its Connor Cares initiative, will continue to expand ... Tour that will commemorate the Indiana Fever legend’s hall-of-fame career and final WNBA ... levels of the game, Connor Sports has committed to a significantly increased focus on ...
(Date:5/26/2016)... ... May 26, 2016 , ... Cardiac arrhythmia is ... impact on long-term patient survival, reports a team of UPMC researchers in the ... in the Journal of Thoracic and Cardiovascular Surgery, provide critical information that will ...
(Date:5/26/2016)... ... May 26, 2016 , ... Catalent ... for drugs, biologics, consumer health and global clinical supply services, today announced two ... support the company’s continued investment and strategic growth plans in the Asia Pacific ...
(Date:5/26/2016)... ... ... to provide hair restoration information to the widest possible audience, Dr. Parsa Mohebi is making ... app. Dr. Mohebi, the founder of Parsa Mohebi Hair Restoration, is making all of his ... says, “The positive response to the Snapchat videos we started last month has been overwhelming. ...
(Date:5/26/2016)... ... May 26, 2016 , ... Eating Recovery Center, Washington ... opening a brand new child and adolescent residential treatment center on June 1. ... even more specialized eating disorder treatment and access to life-saving care. , To ...
Breaking Medicine News(10 mins):
(Date:5/26/2016)... NASHVILLE, Tenn. , May 26, 2016 ... provider of software and analytics, network solutions ... healthcare, today announced it entered into a ... leading provider of outpatient software solutions and ... surgery centers, specialty hospitals and rehabilitation clinics ...
(Date:5/25/2016)... , May 25,2016 ... the near-infrared Cellvizio platform for urological and surgical ... OTCQX: MKEAY) inventor of Cellvizio®, the multidisciplinary confocal ... regulatory milestone in the US with the 12 ... and Drug Administration (FDA). This new FDA clearance ...
(Date:5/25/2016)... GERMANTOWN, Maryland , May 25, 2016 ... bedient dringenden Bedarf zur ... QIAGEN N.V. (NASDAQ: QGEN ; Frankfurt ... und Entwicklungsvereinbarung mit Therawis Diagnostics GmbH zur Entwicklung ... zu sein. Ein erstes Projekt wird die Entwicklung ...
Breaking Medicine Technology: