27/12/2006

Cancer is one of the most important mortality factors worldwide. As part of the new research project, Apotherapy -which is being funded with 2 million euro from the EU's 6th Framework Programme for research and will run from 2007 to 2010- universities, research foundations and biotechnology companies are uniting their experience in the systematic search for new methods of treating cancer. Seven foundations in total from Greece, Great Britain, Germany, Italy, Sweden, the Czech Republic and Finland are taking part in the project, under the coordination of the Laboratory of Molecular and Cellular Biology and associate professor Aristidis Iliopoulos of the Medical School of the University of Crete.

The objective of this research project is the development of a new therapeutic approach for treating epithelial neoplasias, such as those found in the lungs, bladder and ovaries. In particular, the Apotherapy project aims at configuring a therapeutic strategy which will target cancer cells on multiple levels, thus reducing their uncontrolled proliferation and their resistance to chemotherapy, while at the same time strengthening the immunological defence mechanisms against cancer which are naturally developed by the body.

CD40 receptor has a primary role in this strategy; it is a protein present in high quantities on the cellular surface of many types of epithelial cancer. Based on the available experimental data so far, when activated on cancer cells this specific receptor can act suppressively in two ways:
- by immediately suppressing cancer cell proliferation on cells that bear this protein, but also
- by activating the body?s special defence cells, so that they can identify cancer cells and destroy them.

Quite often though, cancer cells develop resistance mechanisms against CD40 cytotoxic action, for example through induction of signalling the PI3K pathway, which is based on the activation of the PI3K molecule (Phosphoinositide 3-kinase). The activation of this pathway has been found in a number of human tumours, indicating that a therapeutic approach based on CD40 anticancer action should guarantee the non-activation of the PI3K pathway. For example, something similar could be achieved by using special inhibitor drugs, the formulation of which has been set out as a goal and main priority by several pharmaceutical companies and research foundations.

The parties involved in the Apotherapy project are given the opportunity to cooperate on the development of gene therapy methods that are aimed at regulated, targeted and selective against cancer cells only, activation of the CD40 receptor and, at the same time, on the formulation of new preparations that will antagonise the PI3K pathway and reduce its effect on cancer proliferation and metastasis. The studies will be carried out both on cell cultures from solid tumours as well as on experimental mouse models, where living samples of cancer proliferation and metastasis will be monitored with in vivo imaging techniques.

The development of such a therapeutic approach is expected to lead to new knowledge that will introduce innovative methods for treating epithelial neoplasias. The project?s long term goal is the practical application of the knowledge accumulated in future clinical studies, to benefit those suffering from cancer.

Source: Laboratory of Molecular and Cellular Biology, Medical School of the University of Crete