More about the Network
Despite substantial progress in the treatment of many cancers, survival rates for patients with squamous cell carcinoma of the oral cavity (OrSCC) have not increased significantly for several decades. The primary reason for this is that OrSCC patients have a strong tendency to develop second primary malignant tumours elsewhere in the upper aerodigestive tract.
It is well known that exposure to environmental carcinogens, chiefly tobacco smoke, greatly increases the risk of OrSCC, but we need greater understanding of the cancer pathogenesis processes involved that lead to tumour development up to several decades after the initial genetic lesion.
This ESF Network has been set up to test an important hypothesis that could greatly increase this understanding and potentially lead to improved prognosis, and both preventative and remedial treatments. This is the idea that both inductive and carcinogen-induced alterations in stromal cell behaviour occur during the process of field cancerisation.
Testing this hypothesis will involve:
1) documenting aberrant stromal cells in apparently normal peri-tumour tissue;
2) assessing the prognostic significance of aberrant stromal cells in a coordinated retrospective study;
3) investigating the effects of well-characterised stromal fibroblasts on target epithelial cells in vitro;
4) collecting data to form the basis of a prospective Network-wide study, which would evaluate the potential for making prognoses by identifying a combination of stromal and epithelial biomarkers.
The field cancerisation hypothesis (FCH) that forms the basis of this ESF Network was formulated by Slaughter et al in 1953, and is defined as the process by which an area of epithelium has been pre-conditioned by some carcinogenic agent. Such an agent if operating for a sufficient combination of intensity and time causes an irreversible change in cells within the given area, making it inevitable that a tumour will eventually develop. This hypothesis implies that cancer develops in a sequence of three events. Firstly, exposure of a sufficiently extensive epithelial field to carcinogen. Secondly, induction by that carcinogen of an irreversible change in epithelial cells throughout the field, and thirdly, the independent development of aberrant epithelial cell foci from these "preconditioned" cells.
It has become clear since its initial formulation that the FCH has enormous clinical implications, including the need for extensive examination to identify more distal peri-tumour tissue in the margins of an excision; the need for rigorous long term monitoring of remaining "condemned" tissue after an operation; and the great potential benefit of chemoprevention strategies.
But a number of questions remain to be answered. For example, although it is known that the progressive acquisition of mutations within the target epithelial cell population plays a central role in cancer pathogenesis, it has also become apparent that other mechanisms operating at higher levels within the tissue are also involved. It has long been recognised, for example, that interactions between epithelial cells and fibroblasts play a key role in the control of cell differentiation and tissue morphogenesis during embryonic development, and also in tissue function during adulthood. Perturbations in these interactions contribute to cancer pathogenesis as well, but further study is needed.
Further study of epithelial-vascular interactions is also essential, as angiogenesis is an essential feature of tumour progression. The establishment of a vascular network associated with a tumour creates a permissive environment for subsequent tumour growth, and this hinges on epithelial-vascular inductive interactions.
This Network was approved by the ESF Executive Council
in September 1997 for a three-year period.
Activities
The network will fund:
Workshops
- some small grants to facilitate the exchange and training of scientists and clinicians to other centres
- sending of material between the participating laboratories
- information dissemination
- workshop at end of the network
