Dr. Eugenie S. Kleinerman
The University of Texas MD Anderson Cancer Center
Departments of Pediatrics and Cancer Biology
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.