Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery of mechanisms predicting response to new treatments in colon cancer

21.05.2012
The Stem Cells and Cancer Research Group headed by Dr Héctor G. Palmer at the Vall d'Hebrón Institute of Oncology (VHIO) has identified the molecular mechanisms that determine patients' response to certain drugs used in clinical trials for colon cancer treatment.

The study led by VHIO also benefited from the collaboration with Professor Alberto Muñoz´s laboratory at the Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Científicas (IIB-CSIC-Madrid).

Published today in Nature Medicine, this work identifies biomarkers that predict response to treatment and proposes therapeutic solutions for patients who do not respond well. These advances will guide better selection of treatments and avoid the risk of administering ineffective drugs.

Colon cancer is a disease caused by a malignant tumour in the large intestine. When detected early the tumor is removed through surgery and patients are treated with adjuvant chemotherapy, eliminating the disease in the majority of cases. However, in advanced stages, colon tumours are resistant to a broad spectrum of anti-tumour drugs and cancerous cells escape treatment and disseminate around the body, giving rise to metastasis. Currently there are no effective treatments to halt the progression of colon cancer in these later stages and most patients die as a result of disease progression.

Over recent years new drugs have been designed to target and block the activity of certain molecules responsible for promoting tumor growth and metastasis. Some of these, which are currently in clinical trials, are showing promising results in certain patients, while others show no improvement at all. This study headed by the VHIO examines the differential response to treatment and was supported by the Olga Torres Foundation (FOT), the Scientific Foundation of the Spanish Association Against Cancer (AECC), and the Carlos III Institute of Health (ISCIII).

New clinical horizons

Dr Héctor G. Palmer´s team has described for the first time the molecular mechanisms through which the interaction between the oncogenic pathways of Wnt/beta-catenin and RAS/PI3K/AKT determines the response to treatments with pharmacological PI3K or AKT inhibitors. Although both pathways are genetically altered in colon cancer, it is the over-accumulation of beta-catenin in the nucleus of cancer cells that makes them resistant to cell death induced by these anti-tumoral drugs.

Activation of the PI3K/AKT pathway retains the FOXO3a protein outside the cell nucleus, inhibiting its ability to act as a tumour suppressor that induces cell death. Therefore, "Targeting PI3K or AKT activity with these novel inhibitors allows relocation of FOXO3a in the nucleus promoting cell death. These drugs are being tested in clinical trials worldwide providing promising initial results in certain tumour types", explains Héctor G. Palmer, Head of VHIO´s Stem Cells and Cancer Group.

However, many colon cancer patients do not show any benefit. The reason for this is explained by Dr Palmer: "If the patients treated with these inhibitors show very high levels of nuclear beta-catenin, FOXO3a cannot induce cell death but promotes the opposite effect by escaping treatment and causing metastasis." According to Héctor Palmer, this finding has tremendous clinical value, since "the identification of nuclear beta-catenin as a biomarker to predict response guides the selection of patients who will benefit from treatment with PI3K or AKT inhibitors and discard their use in candidates who would provoke an adverse response."

Furthermore, Dr Héctor Palmer and his collaborators have discovered a solution for those patients for whom treatment with PI3K or AKT inhibitors would be contraindicated. They used an experimental drug that reduces the levels of nuclear beta-catenin, allowing the cell death induced PI3K or AKT inhibitors. These findings propose the combination of both types of inhibitors in the future for a more effective target-directed therapy in colon cancer.

Delivering on the promise of personalized medicine

VHIO pioneers pre-clinical functional studies and clinical trials in the fight against cancer. Importantly, Dr. Palmer´s team has developed in vivo models that accurately recapitulate disease progression in colon cancer patients. They inoculate the animals with cells derived from the patient's tumour, creating a "xenopatient" model. These cells regenerate the the disease in the animals with the same distinctive characteristics as in the individual patient, retaining its original genetic, clinical and pathological alterations. The xenopatients represent a parallel reality of each patient in the laboratory. This approach allows the study of disease progression and response to experimental medicines before subjecting the patient to new treatments. This model could soon form the basis of future functional, predictive and personalized cancer treatments.

For further information:
Amanda Wren
Communication Manager
Vall d'Hebron Institute of Oncology (VHIO)
Tel. +34 695 207886
e-mail: awren@vhio.net

Amanda Wren | EurekAlert!
Further information:
http://www.vhio.net

More articles from Health and Medicine:

nachricht On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>