| Tuberous Sclerosis may hold the key to a new understanding of Cancer |
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The Tuberous Sclerosis Alliance Reports: "Recent research has found that TSC genes code for two proteins, tuberin and hamartin, which join together to form a tumour suppressor complex, TSC1-2. An article in today's New Scientist by Robin Orwant 'Cancer Unplugged' pp34-37, reports work by Professor Kun-Liang Guan at the University of Michigan that showed for the first time that TSC1-2 is the link between the two pathways important to the growth and division of cells, namely the energy that drives new cell growth and the supply of nutrients, amino acids, needed to make the new proteins. "Newly discovered links between cancer and the way cells grow and manage their energy budget are transforming our view of the disease" says Orwant." "Up until this new work, cancer research mainly focussed on cell division rather than on the mechanisms that cause the cell to grow in the first place. Now researchers have looked at the roles of cellular energy levels, monitored by a protein called AMPK in part of the insulin signalling pathway. In addition signalling through the mTOR (mammalian Target of Rapamycin) pathway controls cellular functions such as cell growth, size and proliferation and is positively regulated by hormones, growth factors and amino acid availability. One of the 'brakes' or negative regulators of mTOR is the Tuberous Sclerosis Complex, and when this is missing as in Tuberous Sclerosis, growth continues unabated."Cell growth has to be co-ordinated to the cellular energy response" says Guan. His team found that when cellular energy levels are low, as signalled by AMPK to mTOR through the TSC protein complex, TSC 1-2, cell growth stops. So problems with AMPK or with TSC 1-2 may encourage tumours to grow. Research reported in June from Yang Ke's group in Beijing showed that the Human Papilloma Virus oncogene, HPV16 E6, implicated in the majority of cervical cancers, may incorporate into human cells by attaching to Tuberin, thus deregulating the TSC1-2 'brake', and causing oncogenesis. There is another negative regulator of mTOR, namely Rapamycin itself. This is currently used as an immunosuppressant to treat transplant patients, and synthetic versions are in clinical trials with cancer patients. It is also hoped that treatment with rapamycin would balance the lack of TSC1-2 found in Tuberous Sclerosis, and prevent increase in growths such as the large kidney tumours. Work will be presented at the Tuberous Sclerosis International Research Conference, September 16-18th, Queens' College, Cambridge that shows one patient whose renal tumour did indeed stop growing, with some decrease in tumour size, suggesting that rapamycin may work in dividing cells. Other papers at the conference will discuss current research in the areas involving TSC proteins, from cardiac hypertrophy to cell adhesion, from regulation of cell differentiation during development to the treatment of the damaged mitochondria in children with TSC that contributes to their cognitive and behavioural problems. A clinical trial in the UK for the treatment by rapamycin of the renal tumours and lung cysts found in TSC is supported by the Tuberous Sclerosis Association. The multi-centre trial has been designed, but the stumbling block is the £400, 000 that the trial will cost, and in particular the estimated £200,000 needed to buy the drug, sirolismus from Wyeth. Until the money is found, this promising trial cannot begin, and the TSA is seeking the support of the public in obtaining this money. Such a trial has implications for the devastating disease, Tuberous Sclerosis, but beyond that to sufferers from cancers that may involve the TSC proteins. " |
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