Gene Function in Tumorigenesis

Rationale - Cancer accounts for more than 1 in 4 deaths in the UK and is the main reason for ongoing research into new, more effective types of cancer treatments that may improve survival and quality of life for cancer patients.  In order to develop better treatments with fewer side effects, we need a more detailed understanding of the underlying mechanisms, both at the DNA and cell level, that give rise to cancer and then drives its spread to other sites throughout the body. By understanding these processes, we can develop more effective and tumour-specific therapies.

We are using mouse models of human cancers including colorectal, breast and liver cancers to look at genes and proteins that promote cancer development. By identifying these, we can develop new drugs to block their function and assess their effects on tumour growth and spread in the most appropriate cancer models. We also use this information to develop nanoparticles (tiny particles around 1 billionth of a metre in size) which can be engineered to deliver drugs specifically to tumours. These nano-drug carriers can deliver drugs directly to a tumour by homing to a tumour-specific marker. Drug release can then be triggered at the tumour site using an external, localised energy source such as ultrasound, thereby sparing healthy tissues from the effects of the drug and minimising unwanted side-effects.

 

Plan of work and impact of our studies - We monitor tumour growth and development in different mouse models.  These have been genetically engineered in some way to determine the effect of particular genes on tumour properties. In addition, mice with weakened immune systems may be used to allow growth of human tumours in mice to better mimic human cancer. We also deliver novel drug formulations and test new treatments in tumour bearing mice to see if growth and/or spread of the tumour can be inhibited. Using a combination of pre-clinical data and studies with human tissues, our aim is to translate novel therapies to first-in-man studies. 

Animal welfare - We use a range of non-invasive imaging techniques on live mice, similar to those used in humans, including ultrasound and MRI, to accurately determine the size and location of tumours. This permits the use of fewer animals and gives a more accurate assessment of tumour burden in vivo allowing us to limit animal suffering as well as providing more relevant and useful data for experimental analysis. 

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