Cancer is the result of uncontrolled cell division. This process involves several cell types, including not only the cancer cells themselves but also the immune cells that have evolved to fight them. Just as the immune system is designed to kill cells infected with viruses, it is able to destroy cancer cells that express mutant proteins, which signify these cells as different and unhealthy. The cancer cells, however, emit inhibitory signals to dampen the immune response. We seek to block these inhibitory signals in order to allow the immune system to perform its natural function of tumor clearance.
Most therapies focus on killing the cancer cells directly with toxic chemicals and/or radiation, but these approaches have severe side effects. More recently, scientists have developed “targeted” therapies that block the proteins in cancer cells that are responsible for stimulating cell division. While these new drugs are strongly preferable to traditional chemotherapy, the molecules go into every cell in the body owing to their physical properties. We have thus developed a delivery system that, like a molecular Trojan Horse, can transfer a novel class of highly specific gene silencers into ovarian cancer cells.
We hypothesize that inhibiting the immunosuppressive signals in concert with the pro-proliferative signals will achieve a synergistic response. This strategy is expected to be relevant broadly across subtypes of ovarian cancer (and ultimately other types of cancer). Moreover, the ability to generate an immune response opens the possibility of having a memory response like that observed upon vaccination; that is, if successful, this approach could lead to a cure rather than simply a transient treatment that may succumb to relapse.
This research has been generously supported by Ovarian Cycle Jackson, MS.
Michael Goldberg, PhD, is an Assistant Professor in the Department of Cancer Immunology & AIDS at the Dana-Farber Cancer Institute.
Dr. Goldberg graduated Summa Cum Laude with an Hon. B.Sc. in Biological Chemistry from the University of Toronto, where he was recognized as a University of Toronto Alumni Association Scholar and “Leader of Tomorrow.” He received an M.Phil. in BioScience Enterprise from the University of Cambridge, where he focused on the critical factors to the development of successful biotechnology clusters. Dr. Goldberg completed his Ph.D. in Biological Chemistry under the supervision of Institute Professor Robert Langer at the Massachusetts Institute of Technology, where he was a member of the founding class of the Harvard-MIT Division of Health Sciences and Technology’s Graduate Education in Medical Sciences program. His doctoral research focused on the synthesis, screening, and application of a novel class of materials for the delivery of RNAi therapeutics. He pursued post-doctoral training in the laboratory of Nobel Laureate and Institute Professor Phillip Sharp in the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, where he worked to develop cancer-specific RNAi therapeutics. His research has been published in leading journals, including Nature and Nature Biotechnology. Dr. Goldberg is the recipient of several awards, including the Bergmann Memorial Research Award, the University College Merit Award, and the Gordon Cressy Student Leadership Award.
His current research interests include cancer immunotherapy and the creation of innovative platforms for drug development and delivery by combining the tools of chemistry, engineering, immunology, molecular biology, and nanotechnology. He seeks to work with the OCRF to develop combination therapies that can silence both genes involved in driving cancers and genes involved in inhibiting the natural immune response against cancer. It is hoped that invoking the immune system could generate a memory response that might constitute a curative intervention.
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