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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
University of Texas MD Anderson Cancer Center
Seeking to improve treatments in advanced triple negative breast cancer (TNBC).
Phase II clinical trial will test a new combination therapy targeting breast cancer stem cells in patients with advanced TNBC.
This work is paving the way to the development of novel therapeutic strategies to improve outcomes for TNBC patients.
Recent discoveries in breast cancer research suggest that breast cancer recurrence may be caused by breast cancer stem-like cells (BCSCs), also called breast cancer-initiating cells. Although these cells make up a small fraction of the tumor, they are resistant to chemotherapy and are capable of metastases (spreading of the tumor to another part of the body). Therefore, targeting BCSCs is an important strategy that could complement standard chemotherapy.
Dr. Andreeff's laboratory previously discovered that BCSCs have a high amount of a cell surface molecule called GD2. Their studies show that cells with high GD2 are better able to detoxify drugs, which may explain their resistance to chemotherapeutic agents. Additionally, analysis of data from the Cancer Genome Atlas revealed that mutations in the tumor suppressor gene, TP53, are commonly seen in GD2-positive BCSCs, suggesting that these mutations could affect BCSC behavior.
The team is working with a drug called dinutuximab, which targets GD2 and is FDA-approved to treat neuroblastoma. Dinutuximab dramatically inhibited growth of tumor cells grown in a dish and in laboratory models.
In the coming year, Dr. Andreeff’s team will implement a phase II clinical trial using dinutuximab (anti-GD2 therapy) to treat patients with stage IV TNBC. They anticipate that these results will lead to the development of a novel therapeutic strategy for targeting BCSCs and improve outcomes in TNBC patients.
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.