Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Molecular Marker Predicts Patients Most Likely to Benefit Longest From Two Popular Cancer Drugs

Published: Wednesday, September 11, 2013
Last Updated: Wednesday, September 11, 2013
Bookmark and Share
Preliminary study needs further confirmation.

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.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

A Simple Blood Test May Catch Early Pancreatic Cancer
Currently, disease usually found too late to save lives.
Wednesday, October 30, 2013
Crucial Brain-Signaling Molecule Requires Coordinated Motion to Turn On
Study could help yield new drugs for brain disorders.
Monday, August 12, 2013
Enzyme-Activating Antibodies Revealed As Marker for Severe Rheumatoid Arthritis
Finding could lead to earlier diagnosis and new, more aggressive treatment for worst cases.
Thursday, May 30, 2013
Researchers Link New Molecular Culprit to Breast Cancer Progression
Johns Hopkins researchers have uncovered a protein “partner” commonly used by breast cancer cells to unlock genes needed for spreading the disease around the body.
Wednesday, November 28, 2012
Scientific News
Charting Kidney Cancer Metabolism
Changes in cell metabolism are increasingly recognized as an important way tumors develop and progress, yet these changes are hard to measure and interpret. A new tool designed by MSK scientists allows users to identify metabolic changes in kidney cancer tumors that may one day be targets for therapy.
"Dark Side" of the Transcriptome
New approach to quantifying gene "read-outs" reveals important variations in protein synthesis and has implications for understanding neurodegenerative diseases.
Advancing Synthetic Biology
Living systems rely on a dizzying variety of chemical reactions essential to development and survival. Most of these involve a specialized class of protein molecules — the enzymes.
Structure of Brain Plaques in Huntington's
Researchers at the University of Pittsburgh School of Medicine have shown that the core of the protein clumps found in the brains of people with Huntington's disease have a distinctive structure, a finding that could shed light on the molecular mechanisms underlying the neurodegenerative disorder.
Visualizing a Cancer Drug Target at Atomic Resolution
Using cryo-electron microscopy, researchers were able to view, in atomic detail, the binding of a potential small molecule drug to a key protein in cancer cells.
Pumpjack" Mechanism for Splitting and Copying DNA
High-resolution structural details of cells' DNA-replicating proteins offer new insight into how these molecular machines function
The Power of Three
Overlooked portion of cell “death receptor” critical in some cancers, autoimmune diseases.
Biomarker for Recurring HPV-Linked Oropharyngeal Cancers
A look-back analysis of HPV infection antibodies in patients treated for oropharyngeal (mouth and throat) cancers linked to HPV infection suggests at least one of the antibodies could be useful in identifying those at risk for a recurrence of the cancer, say scientists at the Johns Hopkins University.
Light Signals from Living Cells
Fluorescent protein markers delivered under high pressure.
Cellular 'Relief Valve'
A team led by scientists at The Scripps Research Institute (TSRI) has solved a long-standing mystery in cell biology by showing essentially how a key “relief-valve” in cells does its job.
Scroll Up
Scroll Down
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!