Implications of select TSC2 mutations in cell division and disease progression
RESEARCH PROPOSAL SUMMARY
A tumour is a mass of cells growing out of control. For a tumour to progress into cancer, it must ensure that it has energy to grow quickly. A normal healthy cell has a central protective mechanism that stops new proteins from being made if nutrients are limited. The main protein controlling this, known as Tuberin, is mutated in a large number of tumour disorders. Many different mutations have been found spanning across the various regions of this very large protein. Some mutations result in small lesions that will never progress to cancer, others result in large tumours that never progress but develop in tissues that are critical to the health of the patient, and still others drive tumour growth that can progress to aggressive malignant cancers. Understanding which mutations are capable of forming cancers will allow physicians to treat patients early in an aggressive manner that may prevent cancers from forming. Furthermore, determining why these mutations cause cancers will allow for the multiple drugs to be used to block all pathways being affected at once, thereby decreasing the chance of a patient relapsing.
The Gauld chemistry lab at the University of Windsor uses computer software to predict what proteins look like and how they can interact with other proteins. We will make models of how these mutations affect the Tuberin protein and how that will impact the proteins it normally interacts with to prevent tumour formation. The Porter and Fidalgo da Silva cancer biology labs can take this information and test our predictions using tumour cells, including those from patients. Our long-term goals will use this as a predictive tool whether a tumour will progress, and whether our information will guide combination therapies that are more effective than the current standard of care.
HOW RESEARCH ADVANCES COMMUNITY CANCER CARE
One leading priority of Cancer Care Ontario (CCO) is to lessen the risk of Ontarians developing cancer. The proposed work will reveal the role that the protein Tuberin plays in causing tumours to develop into aggressive cancers. The gene for Tuberin is one that is already sequenced in many genetics labs. Our goal is to determine if this information alone can be a valuable early prediction tool for certain cancers. Importantly, our work will allow researchers to make informed decisions about combination therapies that are most likely to yield successful results in patients with these mutations. This will result in a better quality of life during treatment, and increased probability of response and decreased probability of relapse. Such advancement will have a tremendous impact on survival rates, thereby having high priority for advancing cancer care both regionally and beyond. This work will foster a new emerging collaboration between researchers at the University of Windsor. It also has a high probability of providing results which can translate into clinical practice. Conducting this work in Windsor is important as patients treated locally would have the opportunity to benefit from these results directly, hence improving the quality of cancer care for Windsor/Essex.
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