Skip to Content

'
Eugenie S. Kleinerman, M.D.

Present Title & Affiliation

Primary Appointment

Mary V. and John A. Reilly Distinguished Chair, The University of Texas MD Anderson Cancer Center, Houston, TX
Division Head, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX

Bio Statement

 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 Childrenís 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 Childrenís 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. Kleinermanís 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. Kleinermanís 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 Ewingís 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. Kleinermanís 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 womenís 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

Research Interests

 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 Ewingís 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 Ewingís 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 Ewingís sarcoma growth and development. NOTCH signaling and DLL4 play a critical role as does VEGF165.

Education & Training

Degree-Granting Education

1974 Duke University, Durham, NC, MD, Medicine
1971 Washington University, St. Louis, MO, BA, Biology

Experience/Service

Endowed Positions

Mosbacher Pediatrics Chair, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, 2005-11/2013

Honors and Awards

2014 Hearts of Gold, Women in Health & Medical Science
2010 Distinguished Alumni Award, Washington University
2009 The Otis W. and Pearl L. Walters Faculty Achievement Award in Clinical Research, The University of Texas MD Anderson Cancer Center
2006 Distinguished Medical Alumni Award, Duke University
1999 Business Professional Women of Texas Award
1984 Young Investigator Award in RES Research, Presented at the 21st National Meeting of the Reticuloendothelial Society
1975 Sandoz Award, Duke University
1975 Sheard-Sanford Award

Selected Publications

Peer-Reviewed Original Research Articles

1. Reddy K, Zhou Z, Schadler K, Jia SF, Kleinerman ES. Bone marrow subsets differentiate into endothelial cells and pericytes contributing to Ewing's tumor vessels. Mol Cancer Res 6(6):929-36, 6/2008. PMCID: PMC2441901.
2. Meyers PA, Schwartz CL, Krailo MD, Healey JH, Bernstein ML, Betcher D, Ferguson WS, Gebhardt MC, Goorin AM, Harris M, Kleinerman E, Link MP, Nadel H, Nieder M, Siegal GP, Weiner MA, Wells RJ, Womer RB, Grier HE, Children's Oncology Group. Osteosarcoma: The addition of muramyl tripeptide to chemotherapy improves overall survival. A Report from the Children's Oncology Group. J Clin Oncol 26(4):633-638, 2/1/2008. PMID: 18235123.
3. Reddy K, Cao Y, Zhou Z, Yu L, Jia SF, Kleinerman ES. VEGF(165) expression in the tumor microenvironment influences the differentiation of bone marrow-derived pericytes that contribute to the Ewing's sarcoma vasculature. Angiogenesis 11(3):257-67, 2008. PMCID: PMC2587248.
4. Gordon, N, Koshkina NV, Jia S-F, Khanna C, Mendoza Arnulfo, Worth, LL, Kleinerman ES. Corruption of the Fas pathway delays the pulmonary clearance of murine osteosarcoma cells, enhances their metastatic potential and reduces the effect of aerosol gemcitabine. Clin Cancer Res 13:4503-4510, 2007.
5. Lee TH, Bolontrade MF, Worth LL, Guan H, Ellis LM, Kleinerman ES. Production of VEGF165 by Ewing's sarcoma cells induces vasculogenesis and the incorporation of CD34(+) stem cells into the expanding tumor vasculature. Int J Cancer 119(4):839-46, 8/2006. PMID: 16557578.
6. Guan H, Jia SF, Zhou Z, Stewart J, Kleinerman ES. Herceptin down-regulates HER-2/neu and vascular endothelial growth factor expression and enhances taxol-induced cytotoxicity of human Ewing's sarcoma cells in vitro and in vivo. Clin Cancer Res 11(5):2008-17, 3/2005. PMID: 15756027.
7. Cao Y, Zhou Z, de Crombrugghe B, Nakashima K, Guan H, Duan X, Jia SF, Kleinerman ES. Osterix, a transcription factor for osteoblast differentiation, mediates antitumor activity in murine osteosarcoma. Cancer Res 65(4):1124-8, 2/2005. PMID: 15734992.
8. Lafleur EA, Koshkina NV, Stewart J, Jia SF, Worth LL, Duan X, Kleinerman ES. Increased Fas expression reduces the metastatic potential of human osteosarcoma cells. Clin Cancer Res 10(23):8114-9, 12/2004. PMID: 15585647.
9. Jia SF, Worth LL, Densmore CL, Xu B, Duan X, Kleinerman ES. Aerosol gene therapy with PEI: IL-12 eradicates osteosarcoma lung metastases. Clin Cancer Res 9(9):3462-8, 8/2003. PMID: 12960138.
10. Bolontrade MF, Zhou RR, Kleinerman ES. Vasculogenesis Plays a Role in the Growth of Ewing's Sarcoma in Vivo. Clin Cancer Res 8(11):3622-7, 11/2002. PMID: 12429654.

Last updated: 6/27/2014