E. Antonio Chiocca, M.D., Ph.D.
Professor of Surgery
4 Blackfan Circle
Boston, MA 02115
Malignant gliomas are one of the deadliest forms of cancer. My research laboratory has been interested in the biology of these tumors as well as in finding new therapies against them.
Biologically, we have focused on the role of microRNAs (miR) in altering signaling pathways that affect several phenotypes relevant to tumor malignancy. One example is provided by miR-128 that we have shown to be critical in the self-renewal of these cancer cells through the targeting of at least two of the epigenetic polycomb repressor complex mRNAs (Godlewski et al, Cancer Res. 2008 and Peruzzi et al, in press). Another example is provided by miR-451 that we have shown to be a critical switch, whose expression regulates the decision of the glioma cell to either proliferate or migrate based on nutrient availability, by targeting the bioenergy pathway, LKB1/AMPK/mTOR (Godleswki et al., Mol. Cell, 2010 and Cell Death and Diff. 2010). In fact, glioma migration and invasion represents a phenotype that is the most difficult to treat and that remains poorly understood. In addition to the role that microRNAs play in this process, we have also been interested in a second signaling pathway that appears to be involved in brain tumor cell motility and invasion, represented by glycogen synthase kinase-3 (GSK-3). We have identified drugs and small molecule inhibitors of GSK-3 and have shown their effectiveness in stopping brain tumor invasion and infiltration into the brain in preclinical animal models (Nowicki et al., Neuro-oncol., 2008; Williams et al., Cancer Res, 2011). In addition to understanding the mechanism of how inhibition of GSK-3 stops glioma cell motility, we are also trying to translate these drugs into a clinical trial in humans afflicted by brain tumors.
Finally, we have also worked on development of biological agents as novel antitumor "drugs". One such class of agents is represented by viruses, engineered to be tumor-selective (oncolytic viruses- OV) (Chiocca, Nature Med., 2002). Over the last decade, we have worked on improving the brain tumor selectivity and potency of these agents (Kambara et al., Cancer Res. 2005) as well as on modulating the brain tumor specific immune response that represents a major variable to the efficacy and safety of this therapy (Alvarez-Breckenridge et al, Nature Med., 2012 and Fulci et al., PNAS, 2006). The ultimate goal of these efforts is to proceed to clinical trials in humans with malignant brain tumors.
For a complete listing of publications click here.
Last Update: 10/30/2013