Choroidal melanoma: how do metastases form?
As a national centre of reference for the treatment of choroidal melanoma, a rare eye cancer, Institut Curie is continuing its commitment to better characterise this disease. It is starting a research programme, a PIC3i, financed by its own funds and to a large extent by the generosity of the general public. The goal is to decode a new method of tumour dissemination.
With 500 to 600 new cases diagnosed every year in France, while choroidal melanoma is the more frequent malignant tumour of the eye, it is still relatively rare. Every year, almost 300 new patients with the disease are treated in the Ophthalmology department of Dr Laurence Desjardins at Institut Curie. Nationally, this ophthalmological surgeon coordinates the national network Melachonat for this pathology, under the auspices if INCa and supported by Malakoff Médéric, to fight inequality.
In parallel, research is continuing to better understand the origins of this cancer, how it is disseminated and how the appearance of metastases, which considerably compromise the prognosis, can be prevented. To date, only complete surgical ablation of the metastases seems to be of benefit to the patient. However, this can only be envisaged in 20% of cases.
Another method of dissemination
Rarely present when an initial diagnosis of uveal cancer is given, metastases are discovered in 30% to 50% of patients and can occur up to 10 years after local treatment of the eye tumour. As the eye does not have a lymphatic system, tumour cells are disseminated through the blood. The metastases first appear in the liver in 90% of cases and, more rarely, in the bones, lungs, subcutaneous tissue or other organs.
"We now suspect the existence of another method of dissemination for this cancer", reports Filippo Del Bene, Inserm director of research and head of the Neuronal Circuit Development team (CNRS/Inserm/Institut Curie) and coordinator of this programme. In skin melanoma, Claire Lugassy and Raymond Barnhill (Institut Curie) showed the existence of another pathway for metastases by progressive migration of cancer cells along the external wall of vessels (angiotropism), without entering the blood stream. They called it "extravascular metastatic migration", unlike intravascular dissemination. Recently, these same researchers, pioneers of extravascular migration, proved that this method of propagation may also exist in choroidal melanomas.
"Moreover, as loss of the BAP1 gene is associated with a higher risk of developing metastases in patients, our project will explore the links between BAP1 and this new method of tumour dissemination", adds Filippo Del Bene. He is now planning to develop zebra fish models in order to study metastatic migration of choroidal melanoma cells in vivo and its correlation with the loss of the BAP1 gene. This young scientist will thus be using his knowledge of neuronal circuits in this animal model to explore tumour dissemination in choroidal melanoma. To successfully complete the programme and shed new light on the development of this disease's metastases, the researcher previously focused mainly on fundamental research, will be able to rely on the environment of Institut Curie and the presence of experts in this pathology.
Find out more
Coordinator:
- Filippo Del Bene, Inserm Researcher, head of Neuronal Circuit Development team (CNRS/Inserm/Institut Curie)
Partners
- Marie Schoumacher, leader of a team on choroidal melanoma supported by Siric and the translational research department.
- Raymond Barnhill, Pathology professor, Institut Curie. Université Paris Descartes.
- Claire Lugassy, physiciand and biologist, Institut Curie.
