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BCRF Grantee Since

2012

Area(s) of Focus

Michael Andreeff, MD, PhD

Paul and Mary Haas Chair in Genetics
Professor of Medicine
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
Houston, Texas

Current Research

Recent discoveries in breast cancer research suggest that recurrence or relapse of breast cancer after treatment may be caused by breast cancer stem-like cells (BCSCs) or breast cancer initiating cells. These cells constitute a small fraction of the primary tumor that can self-renew (generate cells with identical function), are resistant to chemotherapeutic drugs, and are capable of metastases. Therefore, targeting BCSCs is an important strategy that could complement standard chemotherapy.

Dr. Andreeff and colleagues recently discovered that GD2, a cell surface ganglioside, identifies tumor-initiating BCSCs. They showed that GD2+ cells from breast cancer cell lines and patient tumor samples possess all characteristics of BCSCs including mammosphere formation and tumor initiation. In addition, they showed that targeting GD3 synthase (GD3S, which is responsible for the synthesis of GD3, a precursor of GD2) expression reduces tumor growth and prolongs the survival of breast tumor-bearing laboratory models.

In the past few months, Dr. Andreeff’s team identified cell signaling mechanisms that regulate GD2 expression and GD2+ cell frequency in breast cancer cells and (2) generated GD2 specific genetically modified chimeric antigen receptors (CAR)-T-cells to target GD2+ cells in patients with breast cancer. CAR-T-cells were successfully tested in the treatment of neuroblastoma and melanoma and achieved disease-free survival in 30% of the patients tested in clinical trials without significant side effects. Dr. Andreeff has also developed next generation GD2 specific CAR-T cells, tested them against breast cancer cells and achieved 10-15% reduction in GD2+ cells in-vitro. In 2013-2014, he aims to target GD2+ cells in breast tumors using pathway-specific small molecule inhibitors and GD2-CAR-T cells. He expects to achieve major reduction in tumor growth and metastases of breast cancer cells in-vivo and anticipates that these novel approaches will pave the way for the development of novel therapeutic tools targeting cancer stem cells in breast cancer.

Mid-Year Summary

Dr. Andreeff’s group is studying breast cancer stem cells (BCSCs) which migrate long distances from the breast tumor and cause cancer metastasis. In previous research, they identified a biological signature that BCSCs have: they are positive for the ganglioside GD2. In their current research they have now identified and are beginning to investigate agents that selectively kill GD2+ cells. Their current progress has shown that at least one agent effectively inhibits GD2+ cells and inhibits metastasis, by removing the enzyme responsible for GD2 synthesis. Dr. Andreeff’s group is testing the effects of this compound on tumor growth and migration, in combination with current chemotherapeutic agents including doxorubicin and paclitaxel, and anticipates that these experiments will lead to better treatments for patients with breast cancer.

Bio

Michael Andreeff, MD, PhD received his medical degree and doctorate from the University of Heidelberg, Germany, and additional training and faculty appointments at the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York, NY, in the Departments of Pathology and Leukemia.

Dr. Andreeff 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 conference on flow cytometry. In 1977 he joined Memorial Sloan-Kettering Cancer Center in New York, NY, became head of the Leukemia Cell Biology and Hematopathology flow cytometry laboratory, organized the first Clinical Cytometry Conference in 1986 and the first Molecular Cytogenetics Conference in 1990.

He is professor of medicine and holds the Paul and Mary Haas Chair in Genetics at MDACC. He has received uninterrupted NCI funding for over 30 years, serves as PI of the P01 grant entitled "The Therapy of AML" participates as PI in MDACC Leukemia, Lymphoma, Ovarian and Breast Cancer SPORE grants, the CML P01 and additional R21 and R01 grants. 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.