Mark M. Moasser, MD
The rational conquest of cancer depends on a basic understanding of the signaling pathways that drive different tumors, identification of the driving oncoproteins within these pathways that are suitable therapeutic targets, and the development of targeted therapies to succesfully inactivate such targets and their pathways, effecting a collapse of the tumorigenic program. Our group has been focusing on two important oncogenic tyrosine kinase families which are leading the way in this endeavour. The oncogenic potential of Src family tyrosine kinases has been recognized for decades, however the molecular mechanisms underlying their tumorigenic functions appear to be complex. Our group has identified and is studying the functions of a novel cell cycle substrate of src kinases aberrantly phosphorylated in human cancers. The functions of this target in cellular physiology and cell transformation and tumor metastases are being studied and its role as an important mediator of src in human cancer is being interrogated. The functions of the HER family of receptor tyrosine kinases in mediating growth factor signaling are now fairly well characterized and their role in mediating human cancer pathogenesis is well established. Extensive studies of the first generation of HER-targeted therapies have shown clinical activities in some subsets of HER-driven cancers, but resistance to HER-targeted therapies is common. Our group has been focusing on whether selective small molecule tyrosine kinase inhibitors are able to inactivate the oncogenic signaling program in HER-driven tumors, and to identify feedback and crosstalk signaling pathways that enable tumors to evade such targeted therapies.