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HSP90: New point of view on melanoma of the eye, at the MUHC
February 20, 2008Ocular 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.
McGill University Health Centre
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.
McGill University Health Centre
Melanoma Current Events and Melanoma News RSSLaser therapy can aggravate skin cancer
High irradiances of low-level laser therapy (LLLT) should not be used over melanomas.
Quarter of a million children in England at risk of skin cancer from sunbeds
An estimated quarter of a million 11-17 year olds in England are being put at increased risk of developing malignant melanoma by using sunbeds, warn researchers in a letter to this week's BMJ.
Hundreds of genes distinguish patients likely to survive advanced melanoma
Although the chances of surviving advanced melanoma aren't very good with current therapies, some patients can live for years with cancer that has spread beyond the skin to other organs.
New Notre Dame study provides insights into the molecular basis of tumor cell behavior
A new study by a team of researchers led by Crislyn D'Souza-Schorey, associate professor of biological sciences at the University of Notre Dame, sheds light on the molecular basis by which tumor cells modulate their surroundings to favor cancer progression.
Switching immunosuppressants reduces cancer risk in kidney
Switching to a newer type of immunosuppressant drug may reduce the high rate of skin cancer after kidney transplantation, according to research being presented at the American Society of Nephrology's 42nd Annual Meeting and Scientific Exposition in San Diego, CA.
Cancer survivors may not be getting the help they need to stop smoking
More than a quarter of cancer survivors who still smoke have not been advised to quit smoking by their health care providers in the last year, according to a study published by researchers at Fox Chase Cancer Center in the current issue of the Journal of General Internal Medicine.
Melanoma treatment options 1 step closer
A targeted chemotherapy for the treatment of skin cancer is one step closer, after a team of University of Alberta researchers successfully synthesized a natural substance that shows exceptional potential to specifically treat this often fatal disease.
Resident physicians seldom trained in skin cancer examination
Many resident physicians are not trained in skin cancer examinations, nor have they ever observed or practiced the procedure.
New findings on the formation of body pigment
The skin's pigment cells can be formed from completely different cells than has hitherto been thought, a new study from the Swedish medical university Karolinska Institutet shows. The results, which are published in the journal Cell, also mean the discovery of a new kind of stem cell.
Studying cancer in pet dogs to find new treatments for human patients
A team of scientists at the National Cancer Institute (NCI) in Bethesda, USA, says that studying pet dogs with cancer could yield valuable information on how to diagnose and treat human cancers.
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