The Kleinerman Laboratory’s major research interest is developing novel ways to treat sarcoma patients by identifying new therapeutic targets. The Kleinerman Laboratory's research has generated several investigator-initiated protocols which include the use of the immunotherapy liposome-encapsulated MTP-PE in combination with traditional chemotherapy; and either IL-1-alpha, or IFN-gamma in combination with etoposide. L-MTP-PE therapy significantly improved the disease-free and long-term 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 resulted 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 VEGF 165.
The most recent focus is understanding the mechanisms involved in doxorubicin-induced cardiotoxicity and using exercise interventions to prevent both the acute and late heart damage that compromises cardiac function and QOL for childhood cancer survivors.