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Michael Andreeff, MD, PhD
Paul and Mary Haas Chair in Genetics
Chief, Section of Molecular Hematology and Therapy
Professor of Medicine, Department of Leukemia
Professor of Medicine, Department of Stem Cell Transplantation
The University of Texas MD Anderson Cancer Center
Goal: To improve treatments for advanced triple negative breast cancer (TNBC).
Impact: Dr. Andreeff is studying metabolic pathways that are activated in breast cancer stem cells (BCSCs). These cells are thought to drive aggressive tumor behavior and are resistant to chemotherapy. His work may inform the development of novel therapeutic strategies to improve outcomes for patients with TNBC.
What’s next: He and his team will develop a clinical protocol to initiate a phase II clinical trial using anti-GD2 antibody (dinutuximab) in combination with chemotherapeutic agents in patients with TNBC whose cancer has spread to other tissues in their body. GD2 is a new target they discovered on BCSCs that is most highly expressed in TNBC.
TNBC is difficult to treat due to a lack of targeted therapies and resistance of TNBC tumors to several drugs. Dr. Andreeff has identified a new target on breast cancer stem-like cells (BCSCs) that are resistant to chemotherapy and are capable of metastasizing (spreading the tumor to other parts of the body). The target, called GD2, is highly expressed in TNBC. He and his team are now testing a drug called dinutuximab, which dramatically inhibited tumor grown in laboratory models of TNBC, and other compounds that block GD2.
Full Research Summary
Research area: Identifying ways to target breast cancer stem cells (BCSCs) in patients with triple negative breast cancer (TNBC).
Impact: While targeted therapies are available for several subtypes of breast cancer, there are few approved for TNBC, which is aggressive and difficult to treat. Chemotherapy is standard-of-care, but many patients become resistant to this treatment. Dr. Andreeff is investigating ways to target BCSCs, which are believed to drive aggressive tumor behavior. His findings could lead to the development of new targeted therapies for TNBC.
Current investigation: He and his team are focused on GD2, a new target they identified on BCSCs that is most highly expressed in TNBC. They have been developing strategies to eliminate these cells using an immunotherapeutic antibody that is FDA-approved for treating neuroblastoma.
What he’s learned so far: Dr. Andreeff has identified metabolic pathways that regulate the function of GD-positive breast cancer stem cells. His preliminary data suggests that glutathione—an important metabolite that regulates numerous cellular functions, including detoxification, drug resistance, and synthesis of amino acids and DNA—is highly upregulated (increased in expression) in GD2-positive BCSCs. Additional laboratory experiments suggest that blocking glutaminase inhibits BCSC function.
What’s next: Dr. Andreeff and his colleagues are developing a clinical protocol to initiate a phase II clinical trial using anti-GD2 antibody (dinutuximab) in combination with chemotherapeutic agents in patients with metastatic TNBC. They will couple this to laboratory experiments to determine the role of glutamine in the biosynthesis of GD2 in BCSCs and demonstrate the activity of glutaminase inhibitors against BCSCs.
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.