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

Study Finds Potential to Match Tumors with Known Cancer Drugs

Published: Friday, February 08, 2013
Last Updated: Friday, February 08, 2013
Bookmark and Share
Mapping the landscape of kinases could aid in new world of personalized cancer treatment.

When it comes to gene sequencing and personalized medicine for cancer, spotting an aberrant kinase is a home run. The proteins are relatively easy to target with drugs and plenty of kinase inhibitors already exist.

Now in a new study, University of Michigan Comprehensive Cancer Center researchers assess the complete landscape of a cancer’s “kinome” expression and determine which kinases are acting up in a particular tumor. They go on to show that those particular kinases can be targeted with drugs – potentially combining multiple drugs to target multiple kinases.

“We have a small but effective inventory of ‘druggable’ mutations that we know play a role in cancer. As we are doing more sequencing, we’re coming to realize just how small that inventory is. On the one hand, it’s a limitation. On the other hand, there are numerous oncogenic kinases, and there are a lot of kinase inhibitors. Our goal is to determine how to match more of these therapies with the right patients,” says senior study author Chandan Kumar-Sinha, Ph.D., research assistant professor at the Michigan Center for Translational Pathology.

The researchers looked at RNA sequencing data from 482 samples of both cancerous and non-cancerous tissue and identified the most highly expressed kinases in individual breast cancer and pancreatic cancer samples. They found certain common themes.

“A lot of samples showed one or two kinases that showed an outstandingly high ‘outlier’ expression,” says Kumar-Sinha. It wasn’t that the researchers always found a mutation – just that one or more kinases were expressed at a far higher level than all other kinases.

“We don’t always know what’s causing it to be overexpressed. But since it’s there, we know that somehow the high expression of oncogenic kinases is advantageous to the cancer, and so we can therapeutically exploit that dependency,” Kumar-Sinha says.

Results of the study appear online in the journal Cancer Discovery.

In breast cancer, the researchers spotted outlier expression of ERBB2 kinase in HER2-positive tumors, which would be expected. HER2-positive tumors can be treated with Herceptin. But they also found another kinase, called FGFR4 – and they found that adding a drug that blocks FGFR4, in combination with Herceptin, improved the anti-cancer effect. This was done only in cells in the laboratory, but the FGFR4-inhibitor continued to be effective in cells even after they became resistant to Herceptin.

In the pancreatic cancer samples, the researchers found several different kinases that have drugs that work against them, including MET, AKT and PLK. Pancreatic cancer is one of the most deadly types of cancer, often diagnosed in its late stages when treatments are not very effective. The main driver of pancreatic cancer, a mutation in a gene called KRAS, has proven difficult to target with treatments.

In the lab, researchers blocked the outlier kinases and found it had an effect against the cancer cells. They then blocked KRAS – something that can be done in the lab but has not been achieved in patients with pancreatic cancer – and found an even larger effect.

“If in the future we could target KRAS in patients and also hit the outlier kinases, it could have a huge impact on treatment of pancreatic cancer,” Kumar-Sinha says.

These findings must still be tested in patients, but researchers are hopeful that targeting specific kinases expressed in an individual patient’s tumor could make a difference.

The U-M Comprehensive Cancer Center is currently using gene sequencing techniques to help match advanced cancer patients with potential clinical trial opportunities based on the make-up of their tumor.

“We hope kinases will represent another available avenue with whole genome sequencing. If we can identify rational multiple targets for treatment, it’s more effective. This gets us one of those targets,” Kumar-Sinha says.


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 3,400+ scientific posters on ePosters
  • More than 4,900+ 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 New Factor in Depression?
Study in humans & rats shows more physical changes in depressed brains.
Thursday, September 10, 2015
A Roadblock to Personalized Cancer Care
Experts call for more support for tumor biomarker tests; fixing a vicious cycle will lead to tests that better predict treatment success.
Tuesday, August 06, 2013
Scientific News
Adoption of Three Dimensional Culture Models May Save Lives
Physiologically relevant cell models can detect chronic hepatotoxicity early in the drug discovery process.
Molecule Prevents Effect of Chemotherapy
Danish researchers from Aarhus University Hospital and Aarhus University have made a possible breakthrough in the treatment of colorectal cancer.
Hope for Zika Treatment Found in Drug Screening
Johns Hopkins researchers join collaborative group to screen 6,000 existing drugs in hopes of finding treatments for Zika Virus infection.
'Missing Evolutionary Link' of a Widely Used Natural Drug Source Found
A well-known family of natural compounds, called “terpenoids,” have a curious evolutionary origin. In particular, one question relevant to future drug discovery has puzzled scientists: exactly how does Nature make these molecules?
New Possibilities Tumor Research
Grazer researchers say gene activity of the tumor from the analysis of circulating DNA in blood ahead.
Game Changing Antibacterial Drug Research
Researchers publish report on the synthesis of a newly discovered “game-changing” antibiotic, Teixobactin.
New Hope for Zika Treatment Found in Large-Scale Screen of Existing Drugs
Johns Hopkins researchers join collaborative group to screen 6,000 existing drugs in hopes of finding treatments for Zika Virus infection
Mechanisms of Calcium Blockers
Researchers describe how the fundamental mode of action of two distinct chemical classes of calcium channel blockers differs.
Breakthrough in GPCR Understanding
Integral Molecular announces breakthrough in understanding the functionality of GPCRs, the largest class of drug targets in human disease.
Enzyme that Triggers Cell Demise in ALS Identified
Scientists from Harvard have identified a key instigator of nerve cell damage in people with amyotrophic lateral sclerosis (ALS).
SELECTBIO

SELECTBIO Market Reports
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
3,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!