Project award: Prevention of renal lesions by fine-tuning mTOR signalling in a mouse model of Tuberous Sclerosis

Grant holder: Dr Ming Hong Shen
: Institute of Cancer and Genetics, Cardiff University 

Project status: Ongoing – due to finish 31 Dec 2018

In healthy individuals who do not have TSC, the products of the TSC1 and TSC2 gene work together to keep cell division in check. They do this by switching off a component of the cell called mTOR that, if improperly regulated stimulates cell growth and multiplication. In individuals with TSC this switching off mechanism does not work properly and mTOR signals the cells to grow and multiply inappropriately. This can lead to the development of tumours, or overgrowths of cells in many organs of the body. The drug rapamycin has been developed that can inhibit (work against) mTOR, putting the break on cell division in tumours. Although it can shrink kidney tumours in people with TSC, the tumours do not disappear and when treatment is stopped they can regrow.

Dr Shen and his colleagues have shown that it is possible to block the development of tumours in TSC mice before they develop by treating the mice with rapamycin from as early as one month of age. However, rapamycin has a serious side effect when used at the dose needed to stop tumour growth – it also stunts normal bodily growth.

Dr Shen will test whether it is possible to stop the growth of tumours using a lower dose of rapamycin in combination with other drugs known to have anticancer effects. These are called polyphenols. If the study is successful it could lead to the development of treatments that can be given to infants and young children to prevent the growth of tumours without affecting the normal growth of the child.

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