Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
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

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 3,300+ scientific posters on ePosters
  • More than 4,800+ 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
Liquid Biopsies: Miracle Diagnostic or Next New Fad?
Thanks to the development of highly specific gene-amplification and sequencing technologies liquid biopsies access more biomarkers relevant to more cancers than ever before.
Discovered Through ‘Big Data’ Analysis
Researchers at the SBP have identified over 100 new genetic regions that affect the immune response to cancer.
New Therapeutic Targets For Small Cell Lung Cancer Identified
Researchers at UTSW Medical Center have identified a protein termed ASCL1 that is essential to the development of small cell lung cancer and that, when deleted in the lungs of mice, prevents the cancer from forming.
Deciphering Inactive X Chromosomes
Untangling the Barr body of inactive X chromosomes valuable for understanding chromosome structure and gene expression.
Micro Disease-Detecting Senor Created
Researchers at McMaster University have created a microscopic disease-detecting sensor that can turn on to detect trace amounts of substances.
Liquid Biopsies Treating Ovarian Cancer
Researchers have discovered a promising monitor and treat recurrence of ovarian cancer. Detecting cancer long before tumours reappear.
Uncovering a New Principle in Chemotherapy Resistance in Breast Cancer
The NIH study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.
Understanding Treatment Resistant Melanoma
Researchers have determined how advanced melanoma becomes resistant; a development toward developing treatments.
Investigating ‘Black Box’ of Human Genetics
Investigations into inactive X chromosomes have shown unusual DNA repeat elements are essential for maintaining 3D structure.
Liquid Biopsies: DNA Size Matters
Study finds circulating tumour DNA can be distinguished from healthy DNA through fragment size identification.
Skyscraper Banner

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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!