Corporate Banner
Satellite Banner
Genotyping & Gene Expression
Scientific Community
Become a Member | Sign in
Home>News>This Article

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 2,800+ scientific posters on ePosters
  • More than 4,000+ 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 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
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Mathematical Model Forecasts the Path of Breast Cancer
Chances of survival depend on which organs breast cancer tumors colonize first.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Measuring microRNAs in Blood to Speed Cancer Detection
A simple, ultrasensitive microRNA sensor holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
Personalized Drug Screening for Multiple Myeloma Patients
A personalized method for testing the effectiveness of drugs that treat multiple myeloma may predict quickly and more accurately the best treatments for individual patients with the bone marrow cancer.
Metabolic Profiles Distinguish Early Stage Ovarian Cancer with Unprecedented Accuracy
Studying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.
New Way to Force Stem Cells to Become Bone Cells
Potential therapies based on this discovery could help people heal bone injuries or set hardware, such as replacement knees and hips.
Promise of Newborn Stem Cells to Revolutionize Clinical Practice
In this article Shweta Sharma, PhD, discusses the potential of an Umbilical Cord Blood bank as an untapped source of samples for research and clinical trials.
New Anti-Malarial Drug Screening Model
University of South Florida researchers demonstrate novel chemogenomic profiling to identify drug targets for the most lethal strain of malaria.
Coronavirus Breakthrough
Protein mutation affects spread and virulence of respiratory virus.
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos