New drug therapies to kill Tsc2-deficient cell lines

Grant holder: Dr Andrew Tee (Henry McCann)
: Institute of Cancer and Genetics, Cardiff University

Project status: Ongoing – due to finish 20 Sept 2018

Tuberous Sclerosis (TS) patients are a high risk group for developing kidney tumours (60-80%), which is caused through mutation of either the Tuberous Sclerosis Complex 1 or 2 (TSC2) genes. While these kidney tumours are often removed through surgical techniques, having a non-invasive therapy that specifically kills these TS-associated tumour cells would be extremely valuable to TS patients. 

It is hoped that such new drug therapies could improve the healthcare of TS patients by lessening the need for surgical intervention. Dr Tee and colleagues recently discovered that the clinically approved drug, nelfinavir, selectively killed the fast growing Tsc2-associated tumour cells, while the normal healthy cells were relatively unaffected. Of importance, they were able to further improve nelfinavir’s potency to kill Tsc2-compromised tumour cells when combined with another already clinically approved drug, bortezomib. 
This project will test the effectiveness of these new potential combination therapies to selectively kill TSC-associated tumour cells. Such experimentation will allow researchers to fine-tune drug therapies to determine the optimum drug combination to kill tumour cells whilst maintaining low toxicity to healthy cells. This project is designed to provide the necessary data to support future pre-clinical studies in TS model systems and also clinical studies in TS patients, of which the research team have a strong track record. 

This work also has important implications for cancer patients with Tsc2-compromised tumours, such as those with kidney, lung, bladder, breast and colon cancers. Although the first priority is to improve healthcare for TS patients, this project could also benefit a wide range of cancer patients within the general population.

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