HSP90: new point of view on melanoma of the eye, at the MUHC
Ocular melanoma is rarely detected before it has grown large enough to impair vision or to metastasize. This makes it a particularly challenging disease to fight, especially since chemotherapy is not very effective. Now, the PhD research project led by Dr. Dana Faingold may open the door for very promising new treatment options for this pathology. Her first article was featured on the cover of the February 2008 issue of Clinical Cancer Research.
"The first step in developing a medication is to determine the precise target of action," explained Dana Faingold. "In this study, we have shown that to effectively fight this malignant tumour in the vascular network of the eye, we had to target Heat Shock Protein 90 (HSP90)."
HSP90 is already a therapeutic target in many other types of cancer. In fact, this protein, which is called a "chaperone" because it guides the actions of other proteins, is at the centre of many metabolic pathways. By disrupting HSP90's functioning, it is possible to affect multiple steps in cell metabolism, for example, signalling pathways, cell cycle regulation pathways, or growth hormone receptors. This blocks many vital cellular functions, so the cancer cells become unable to reproduce and the tumour regresses.
Clinical trials are currently being conducted to determine the effectiveness of an antibiotic called 17/AAG, an HSP90 inhibitor, against malignant tumours of the skin, breast and in patients with multiple cancers. However, no one has yet studied this inhibitor's effect on ocular melanoma. "This is a pre-clinical study, which means we are examining in-vitro cell lines. Our results clearly prove not only that HSP90 is largely overexpressed in this type of tumour but also that the 17/AAG molecule is effective at reducing the growth of these tumoral cells," said Dana Faingold.
Several clinical trial stages will have to be completed before 17/AAG can be recognized as a possible treatment for melanoma of the eye. The first stage, which should begin shortly, aims at proving the effectiveness of the molecule in an animal model. This in vivo confirmation is necessary before testing for human treatment can begin.
Dana Faingold is a doctoral student in the Henry C. Witelson Ocular Pathology Laboratory of the Research Institute of the Ï㽶ÊÓƵ Health Centre.
This study was funded through a Henry R. Shibata Fellowship Grant from the Cedars Cancer Institute.
The Research Institute of the Ï㽶ÊÓƵ Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, a university health center affiliated with the Faculty of Medicine at Ï㽶ÊÓƵ. The institute supports over 500 researchers, nearly 1000 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge. For further details visit: .
