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Human cells continuously grow and divide to replace old ones that have passed their ‘sell by date’. This process is normally tightly controlled by multiple complex mechanisms, however sometimes it can go wrong, and cells can grow out of control. This is how cancer develops. My project involves looking at genes called ‘PI3Ks’, which play a key role in this control of cell growth and division. I am currently looking at the role these genes play in lung cancer, how they communicate with other genes involved in growth and how the cells behave if we inhibit one or more of these genes through drug intervention. Several new drugs targeting these PI3K genes are currently being investigated in lung cancer patients. I am carrying out experiments on cancer cells in the laboratory, as well as on tissue samples donated by lung cancer patients here in St. James’s Hospital, to determine how best to utilise these drugs. Unfortunately, after a certain length of time, most patients who initially responded well to treatment with PI3K inhibitors can become resistant to the effects of the drugs. We have developed our own panel of PI3K inhibitor resistant cell lines, and we are utilising state of the art technologies such as High Content Analysis (HCA), next-generation sequencing, Fluorescence-activated cell sorting (FACS), Xcelligence, gene arrays and protein arrays to fully investigate the best ways to overcome or avoid this development of resistance. This will ultimately allow us to better design treatment strategies for lung cancer patients, possibly involving the use of PI3K inhibitors in combination with other types of drugs, in individually tailored and personalised treatment regimens.
The development of drug resistance by cancer cells is a serious problem which scientists are trying to understand and find a solution for. This project focused on a group of anti-cancer drugs, called PI3K inhibitors, which can be used to treat certain lung cancer patients. The aim of this study is to find ways of predicting which lung patients will respond to PI3K treatment, and which will not.
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