Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

COLTHERES Consortium Identifies Molecular Signatures Leading to Personalized Therapies for Colorectal Patients

Published: Thursday, October 25, 2012
Last Updated: Wednesday, October 24, 2012
Bookmark and Share
18 month report also includes evidence to support novel therapeutic approaches.

COLTHERES (the Colon Therapy Research Consortium) has revealed in its first interim report key results that will enable a more personalized and effective approach to be taken in treatment of colon cancer using two novel drugs; the EGFR inhibitor Cetuximab and the BRaf inhibitor Vemurafinib.

COLTHERES is a four year project, which was established with funding from the EU Framework-7 program, to uncover new genetic biomarkers that will predict which patients are most likely to respond to a range of new targeted therapies in colon cancer and whether the majority of patients who are resistant can be rendered sensitive again using specific drug combinations.

COLTHERES integrates experts in biomarker-driven clinical trials, genomics, functional genomics, and isogenic disease model generation using rAAV-mediated genome editing, to comprehensively identify, validate and translate new candidate biomarkers of drug response and novel drug combinations into the clinical setting.

The key findings detailed in the interim report were:

• Identification of biomarkers in patients resistant to EGFR targeted therapies, to enable a more personalized approach to therapy

Building on seminal founding studies by members of the COLTHERES consortium, which showed that activating mutations in KRAS are the cause of resistance to EGFR-inhibitors in 30-40% of colon cancer patients, the consortium has now identified additional biomarkers in a further 30-40% of patients who are resistant to Cetuximab.

These include mutations in key downstream molecules, over-expression of activating or competing molecules, or loss of pathway inhibitors which, when combined with a global gene expression signature also developed by the team, will form a far more comprehensive ability to identify responders to Cetuximab treatment than by KRAS mutations alone.

• Molecular evidence to support an alternative therapeutic approach for BRAF mutant patients

The consortium has also identified why some BRAF mutant colon cancer patients, in stark contrast to melanoma patients, are unresponsive to Vemurafenib therapy (an inhibitor of BRAF). In this case, a rapid feedback activation of the EGFR receptor was found in colon cancers that are being treated with Vemurafinib, which opens up the possibility that a targeted combination of an EGFR-inhibitor and Vemurafinib may now allow a robust response in these patients. In vitro and preclinical data are encouraging in this regard and a clinical trial is now the planning stages.

• Validation of a new diagnostic technique for early prediction of patient relapse

A cutting-edge diagnostic technique called ‘BEAMing’ has been used by the Consortium to monitor and analyze tumor DNA over time in the blood of patients who are initially responsive to treatment, enabling the detection of secondary ‘acquired’ mutations in the KRAS gene that are causally associated with acquired resistance to targeted therapies for colorectal cancer.

As these mutations can be detected using simple non-invasive liquid biopsies, and critically several months before radiographic evidence of disease progression is observable, clinicians can anticipate and counter resistance using targeted drug combinations before the patient relapses.

Prof. Alberto Bardelli, IRCC University of Torino, co-founder Horizon Discovery Ltd and Lead Investigator of COLTHERES, said: “In its first 18 months COLTHERES has exceeded our expectations; defining new molecular markers leading to personalized therapies for colorectal cancer patients and providing data for use as the basis of innovative clinical trials. The expertise and technologies offered by the consortium members have made this possible, and we anticipate further breakthroughs in the remainder of the project term.”

Members of the COLTHERES consortium have jointly authored a number of publications in high profile journals such as Nature over the first 18 months of the program, and results have been presented at international meetings such as AACR, ESMO and ASCO.


Further Information
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 2,500+ scientific posters on ePosters
  • More Than 3,700+ 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.


Scientific News
NIH Study Finds Calorie Restriction Lowers Some Risk Factors for Age-Related Diseases
Two-year trial did not produce expected metabolic changes, but influenced other life span markers.
Immunotherapy Agent Benefits Patients with Drug-Resistant Multiple Myeloma in First Human Trial
Daratumumab proved generally safe in patients, even at the highest doses.
Low-level Arsenic Exposure Before Birth Associated with Early Puberty in Female Mice
Study examine whether low-dose arsenic exposure could have similar health outcomes in humans.
Inciting an Immune Attack On Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
‘Mutation-Tracking’ Blood Test for Breast Cancer
Scientists have developed a blood test for breast cancer able to identify which patients will suffer a relapse after treatment, months before tumours are visible on hospital scans.
Cellular Contamination Pathway for Heavy Elements Identified
Berkeley Lab scientists find that an iron-binding protein can transport actinides into cells.
Intensity of Desert Storms May Affect Ocean Phytoplankton
MIT study finds phytoplankton are extremely sensitive to changing levels of desert dust.
Common ‘Heart Attack’ Blood Test May Predict Future Hypertension
Small rises in troponin levels may have value as markers for subclinical heart damage and high blood pressure.
LaVision BioTec Reports on the Neuro Research on the Human Brain After Trauma
Company reports on the work of Dr Ali Ertürk from the Institute for Stroke and Dementia Research at LMU Munich.
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
Scroll Up
Scroll Down
Skyscraper Banner

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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!