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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 RSSChildren's National researchers develop novel anti-tumor vaccine
A novel anti-tumor vaccine for neuroblastoma and melanoma developed by scientists and clinicians at Children's National Medical Center in collaboration with investigators from the University of Iowa is showing significant impact on tumor growth in mice.
Researchers identify mechanism used by gene to promote metastasis in human cancer cells
Virginia Commonwealth University Institute of Molecular Medicine and VCU Massey Cancer Center researchers have discovered how a gene, melanoma differentiation associated gene-9/syntenin (mda-9/syntenin), interacts with an important signaling protein to promote metastasis in human melanoma cells, a discovery that could one day lead to the development of the next generation of anti-metastatic drugs for melanoma and other cancers.
Social class dictates cancer risk
Cervical and lung cancer are more common in poor people while rates of breast cancer and melanoma are higher in the wealthy.
Variant of vitamin D receptor gene linked to melanoma risk
A new analysis indicates an association between a gene involved in vitamin D metabolism and skin cancer. Published in the November 1, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study suggests that individuals with certain variants in a vitamin D-related gene, called BsmI, may be at an increased risk of developing melanoma.
Wistar researchers invigorate 'exhausted' immune cells
In battles against chronic infections, the body's key immune cells often become exhausted and ineffective. Researchers at The Wistar Institute have found a way to restore vigor to these killer T cells by blocking a key receptor on their surface, findings that may advance the development of new therapies for diseases such as HIV, hepatitis B and C, and cancer.
Nanomedical approach targets multiple cancer genes, shrinks tumors more effectively
Nanoparticles filled with a drug that targets two genes that trigger melanoma could offer a potential cure for this deadly disease, according to cancer researchers.
History of nonmelanoma skin cancer is associated with increased risk for subsequent malignancies
Individuals with a history of nonmelanoma skin cancer (NMSC) are at increased risk for other cancers, according to a study published in the August 26 online issue of the Journal of the National Cancer Institute.
Researchers discover scent of skin cancer
According to new research from the Monell Center, odors from skin can be used to identify basal cell carcinoma, the most common form of skin cancer. The findings, presented at the 236th meeting of the American Chemical Society, may open doors to development of new methods to detect basal cell carcinoma and other forms of skin cancer.
Fish cancer gene linked to pigment pattern that attracts mates
Though skin cancer is deadly to male fish, it also has one perk: The black melanoma splotches arise from attractive natural markings that lure female mates. A new study published in the Proceedings of the National Academy of Sciences this week shows that the melanoma gene can be conserved in swordtail fish because of its beneficial role in sexual selection.
Prototype test for predicting clinical outcome for melanoma patients
Investigators from the Melbourne Center of the international Ludwig Institute for Cancer Research (LICR) and Pacific Edge Biotchnology Ltd today reported that they have developed a test to predict whether a patient will progress rapidly from Stage III melanoma to metastatic Stage IV cancer and death.
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