Exploring c-Met and HER3 crosstalk by nano-proximity imaging for understanding its clinical significance in lung adenocarcinoma.

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Lung cancer has a long-standing reputation of being difficult to treat, particularly since it is often identified after spread to other organs. However, doctors and lung cancer scientists have become very excited about a new type of targeted therapy known as a "cancer growth blocker", that blocks the interaction between natural chemicals in the body controlling growth ("growth factors") with the part of the cell that receives the signal of these growth factors. Such growth signals are produced uncontrollably by cancer cells so that drugs blocking the signal could be a highly effective way to block cancer growth. In fact, these drugs are now commonly used in a several types of cancer including a form of lung cancer called "Non-small cell lung cancer". One particularly important example are drugs that block one of the main signal receivers or "receptors" - known as the "epidermal growth factor receptor" - e.g. Gefitinb or Erlotinib, which have considerably improved the life expectancy of lung cancer sufferers.Unfortunately the cancer often becomes resistant to these drugs by finding other ways to communicate the message from the growth factors via different receptors i.e. if one receptor is blocked by drug, with time, another receptor can start receiving the same signal, which means the treatments stop working i.e. "treatment resistance". I will use a special type of microscope that uses "FLIM" (Fluorescence Lifetime Imaging Microscopy) that allows us to see how these receptors are located in the cell and how active they are in response to treatment. I will then use cells from tumours of different patients (that have or have not developed resistance) to test a new "inhibitor" against a different type of receptor "c-Met" because there is some good evidence to suggest its importance in lung cancer signalling, particularly if the cancer is resistant to other treatments. These cells can then be injected into a small number of mice that can be treated with the drugs to see how the cancer behaves in a living organism. I will then use this special microscope to examine the tumours formed and the effect of this drug in mice, and later on in biopsy specimens from patients, to predict response to the drug. One of the most important findings will be understanding treatment resistance in more detail. This will also allow us to identify patients that will benefit from the use of new drugs that may beat resistance, without subjecting others to the side effects if they are not suited to their type of cancer.In the future, such information would be useful to other scientists developing ways of predicting lung cancer responsiveness to treatment to focus the patients who will benefit most from them. This could make drug trials more affordable and potentially more accessible for patients, thus avoiding waste in a time when resources are scarce.This research will be conducted by a research doctor training at a higher level in respiratory medicine who has a particular interest in caring for patients with lung cancer. The research team will also include a senior chest physician with expertise in lung cancer research and a professor of oncology. This research will be largely based in the laboratory, studying cells and mice using very specialised microscopes. In addition, an important part of the study will be on samples that patients have donated to research including lung tumours that have been operated on but also materials coming from glands that will give us unique information about why cancer spreads.This is an exciting area in lung cancer research which has the opportunity to help patients in a disease which can be extremely difficult to treat and can leave patients with life expectancies of less than six months at diagnosis. In patients in whom the treatment has stopped working where life expectancy can be be extremely poor, this kind of approach could offer a new lease of life to those with weeks or months to live.