Proteolytic signatures and networks in breast cancer metastases

Breast cancer is the second most common form of cancer. A crucial event in the development of the disease is when cells start to leave the breast tumour, enter the bloodstream and start to form a new tumour in other organs, such as the lung and bone. This process, called metastasis, dramatically reduces the patient's chances of disease recovery. Hence, in depth understanding of this process is key to successful development of novel anti-cancer drugs to provide effective treatment for cancer patients. Although the genetic changes that cause cancer to develop and metastasize are being studied, there are other molecular events that contribute to cancer. The post-translational modification of proteins — which refers to the changes that occur after the proteins are built — can dramatically alter the protein function, putting it in a different place or switching the activity on or off. One way to modify a protein is to cleave a part of it off, exposing a new protein """"tail.” Identification of the actual modification patterns in different disease situations will presumably allow for a much more precise disease diagnosis. Knowing the protein differences between metastases, which are surprisingly different from the tumours they originate from, will help to identify the fundamental causes and provide great insight into the cellular processes affected during cancer. Dr. Philipp Lange's research involves the identification of protein """"tails"""" in different cancer tumours and metastases in order to identify differences between the two. He will also introduce a new protein into the tumours that can mediate the cleavage reactions in a controlled manner, which will enable him to deduce how the individual protein components of tumours were originally connected. As a final step in his research, he will investigate the key protein modification patterns (or """"signatures"""") found in the mouse model and see if this signature exists in patient tumour samples taken from the Tumour Tissue Repository at the BC Cancer Agency. The impact of Dr. Lange's work will be twofold. First, the protein modification signatures he identifies will be used to develop a powerful new method to support earlier breast cancer diagnosis and determination of patient prognosis. Second, the identified key network modulators serve as potential drug targets for the development and testing of new breast cancer therapeutics.