University of Texas MD Anderson Cancer Center Houston, Texas
Paul and Mary Haas Chair in Genetics Chief, Molecular Hematology and Therapy Professor of Medicine, Department of Leukemia Professor of Medicine, Department of Stem Cell Transplantation
Improving treatments for advanced triple negative breast cancer.
While targeted therapies are available for several subtypes of breast cancer, there are few approved for triple-negative breast cancer (TNBC), which is aggressive and difficult to treat. In search of new therapeutic options for TNBC, Dr. Andreeff and his team identified a molecule called GD2 that appears to be specifically overproduced by breast cancer stem cells—a population that may drive tumor growth and therapeutic resistance. The team is exploring how GD2 functions in TNBC and the potential uses of GD2-targeting therapies.
Thus far, the team unveiled several interesting roles for GD2 in TNBC progression. Preliminary data suggest that when GD3 synthase (GD3S), an enzyme that regulates GD2 expression, is overexpressed, it prevents immune cell-mediated killing of TNBC tumor cells. They also found that inhibition of GD3S completely abrogates tumor growth and metastasis in laboratory models. In addition, they identified specific mutations in a gene that encodes for a tumor suppression protein, TP53, that regulates GD3S expression.
In this upcoming year, Dr. Andreeff and his team will continue to explore the mechanistic details of GD2, GD3S, and TP53 using state-of-the-art quantification measurements of TNBC tumors in laboratory models. Their efforts will help elucidate the mechanistic details linking tumor-survival pathways and immune suppression and may establish a preclinical rationale for targeting GD2 and GD3S in TNBC treatment.
Michael Andreeff received his MD and PhD from the University of Heidelberg, Germany, and additional training at Memorial Sloan Kettering Cancer Center. He has been a pioneer in flow cytometry since 1971, when he established the first flow cytometry laboratory at the University of Heidelberg and organized the first European flow cytometry conference. In 1977 he joined MSKCC, became head of the Leukemia Cell Biology and Hematopathology flow cytometry laboratory, and organized the first Clinical Cytometry Conference in 1986. Since 1990 he has been Professor of Medicine at MD Anderson Cancer Center where he holds the Paul and Mary Haas Chair in Genetics. He has published over 450 peer-reviewed papers, 5 books and 75 book chapters.
Dr. Andreeff’s group has worked extensively on drug resistance in hematopoietic malignancies and breast cancer and developed or co-developed several new therapeutic agents including the novel triterpenoids CDDO and CDDO-Me and Bcl-2- , XIAP- , surviving-, MEK- and HDM2- inhibitors. Over the last decade, his group has made major contributions to the understanding of micro-environment-mediated drug resistance and developed strategies to exploit the underlying mechanisms for the treatment of hematopoietic and epithelial malignancies. His group reported the role of bone marrow-derived multipotent mesenchymal stromal cells (MSC) in tumor stroma formation and developed therapeutic strategies based on this discovery.
2012
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