Notch signaling in Lymphoid Neoplasia

A common theme in cancer is the dysregulation of a normal developmental process that either directly causes cells to grow in an uncontrolled manner, or renders them susceptible to cellular damage that, in turn, leads to uncontrolled growth. One example of this process occurs with a normal cellular gene called Notch, which is inappropriately activated in a large fraction of cases of a certain type of blood cancer called T cell acute lymphoblastic leukemia (T-ALL). During normal development of the immune system, regulated Notch activity is required for formation of mature lymphocytes that protect the body from infection. When activated, Notch promotes the formation of normal T lymphocytes, but if this signal is not turned off in time, these T cells can undergo malignant change and become cancerous. Dr. Andrew Weng is studying the signals that are generated by Notch activation and the context in which these signals are received by the cell. By understanding the role of Notch in cancer development, he hopes to develop methods for manipulating Notch activity to shut down the growth of established cancer cells, and perhaps also to prevent it from occurring in the first place.

Tissue microarray analysis of Type 1 growth factor receptor family expression by human breast and colorectal Cancer: prognostic significance and treatment implications

Breast cancer and colorectal cancer are leading causes of cancer-related deaths worldwide. The identification of specific tumor characteristics that would allow for an accurate prediction (prognosticators) of disease course and response to treatment would represent an important advancement in the management of these common malignancies. Unfortunately, no currently known disease prognosticators are reliable in predicting clinical course, or identifying the treatment that would be of greatest benefit to an affected individual. Recently the detection in some tumours of HER1 and HER2 proteins – members of the type 1 growth receptor family (T1GFR) – have shown promise for helping predict patient outcomes and in determining which tumors respond best to specific therapies. These proteins have also recently been used as targets for newly developed drugs to treat these cancers. The expression of the entire T1GFR family (HER1, HER2, HER3, and HER4) by breast and colorectal tumors, and their potential usefulness in predicting disease outcome and patient response to specific treatment(s) has not been explored. Dr. Sam Wiseman is evaluating the expression of the entire T1GFR family in a group of 4500 breast cancer and 500 colorectal cancer samples to determine its relationship to patient treatment and outcomes. His study will be carried out utilizing tissue microarrays, a methodology that allows for the rapid evaluation of large numbers of tumors for molecular markers. The results of this study may lead to improved disease prognostication, outcome prediction, and therapy selection for people diagnosed with breast or colorectal cancer.