Primary Appointment

 Eugenie S. Kleinerman, M.D. is Professor and Head of the Division of Pediatrics, the first women Division Head at M. D. Anderson. She is board certified in pediatrics, holds the Mosbacher Pediatrics Chair and is also a Professor of Cancer Biology. A native of Cleveland, OH, Dr. Kleinerman received her BA degree from Washington University in St. Louis, her medical degree from Duke University, then completed her pediatric residency at the Children’s Hospital National Medical Center in Washington, DC and her fellowship at the National Cancer Institute in Bethesda, MD. She was a Senior Investigator at the NCI-Frederick Cancer Research facility for 3 years before being recruited to M. D. Anderson in 1984. Dr. Kleinerman rose through the ranks from Assistant Professor to Professor and in 2001 was named Head of the Division of Pediatrics.

Dr. Kleinerman is internationally recognized for her scientific and clinical expertise in sarcomas, particularly osteosarcoma. She pioneered the use of a unique immunotherapy agent liposome-encapsulated MTP-PE, for children with unresponsive relapsed osteosarcoma lung metastases. Her phase II clinical trials done at M. D. Anderson demonstrated that liposomal MTP-PE therapy activated the tumoricidal properties of macrophages, prolonged disease-free survival and could be combined with chemotherapy. The success of these trials led to a national phase III trial sponsored by the Children’s Oncology Group. Newly diagnosed osteosarcoma patients treated with liposomal MTP-PE plus chemotherapy has a 30% reduction in mortality rate compared to the patients that received chemotherapy alone. This demonstration of efficacy led to the recent approval of liposomal MTP-PE by the European Medicine Agency, which is now available in 27 countries in the European Union. Dr. Kleinerman’s pioneering use of this immunotherapeutic agent in children with osteosarcoma resulted in the first improvement in long term survival of children with this disease in over 20 years.

Dr. Kleinerman’s laboratory research has also focused on understanding the mechanisms involved in osteosarcoma metastasis to the lung. Her investigations demonstrate that tumor Fas expression and the Fas/FasL pathway play a critical role in the metastatic potential of osteosarcoma cells and that this pathway can be targeted for therapeutic benefit. She is the first to show that Ewing’s tumor vessels are formed by both local endothelial cells and bone marrow cells that have migrated to the tumor and differentiated into endothelial cells and pericytes. Dr. Kleinerman’s research program has been funded by the NCI for over 22 years.

Dr. Kleinerman has served on numerous NCI study sections and was a prior member of an FDA advisory panel. She has authored >155 articles and 21 book chapters. She has mentored numerous graduate students, postdoctoral fellows, MD/PhD students, and physician-scientists. She has worked to promote women and women’s issues in academic medicine. In 2006, her achievements were recognized by her alma mater, Duke University Medical Center, where she received the Distinguished Medical Alumnus Award.  She is the 2009 recipient of the Faculty Achievement Award in Clinical Research

 My major interest is to develop novel ways to treat sarcoma patients by identifying new therapeutic targets in my laboratory and translating these ideas into clinical practice. I generated several investigator-initiated protocols based on my bench research including the use of either liposome-encapsulated MTP-PE, or ImmTher (2 immune therapies) in combination with traditional chemotherapy, and IL-1a, or IFNa in combination with VP-16. L-MTP-PE alone or with ifosfamide significantly improved the disease-free survival of relapsed osteosarcoma (OS) patients. In a phase III trial adding L-MTP-PE to combination chemotherapy reduced the mortality rate of newly diagnosed OS patients by 30%.

Mouse models were developed (for OS and Ewing’s sarcoma) to study the properties that influence metastases and to evaluate therapeutic strategies. We determined that Fas expression influences the metastatic potential of OS cells. We demonstrated the in vivo efficacy of aerosol Liposomal 9-nitrocamptothecin and gemcitabine against OS lung metastases. These agents upregulate the expression of Fas on the tumor cell surface, which results in the elimination of tumor cells by the constitutive FasL expressed in the lung.

Another focus is understanding how tumor vessels are formed in Ewing’s sarcoma. New vessel development is a key component in supporting the growth of solid tumors. We demonstrated that bone marrow (BM) cells are involved in the vascular development and that vasculogenesis, in addition to angiogenesis, plays a role in Ewing’s sarcoma growth and development. NOTCH signaling and DLL4 play a critical role as does VEGF₁₆₅.

Academic Appointments

Last updated: 6/12/2009