Title:Combination Therapy of Intraperitoneal Rapamycin and Convection- Enhanced Delivery of Nanoliposomal CPT-11 in Rodent Orthotopic Brain Tumor Xenografts
Volume: 15
Issue: 4
Author(s): Marina Mendiburu-Elicabe and Jon Gil-Ranedo
Affiliation:
Keywords:
Combination, CPT-11, glioma, rapamycin, therapy.
Abstract: Background: Glioblastoma multiforme (GBM) is the most malignant histological type of
glioma. It exhibits an extremely aggressive action including invasion of large zones of brain parenchyma.
Even after the application of surgery, radio and chemotherapy, the effect and survival for patients
with GBM continue to be very poor. The PI3K/AKT/mTOR is a key pathway in the regulation of the
proliferation of cancer cells. This is the reason to consider the mTOR inhibitors such as rapamycin
analogs as an encouraging therapy for malignant glioma, but current investigations suggest that single inhibition of mTOR
may be insufficient. For this reason, there is a need for the use of more than one agent rationally combined.
Methods: In this study, we have evaluated the therapeutic potential of the combination of two different drugs:
intraperitoneal rapamycin and convection enhanced delivery of nanoliposomes containing the topoisomerase I inhibitor
CPT-11. The effect was analyzed by flow cytometry, cell growth, immunocytochemistry and immunohistochemistry, and
rodent orthotopic xenograft survival analysis.
Results: The combination presented remarkable efficacy in a survival study. We present an increase in survival of 6-fold
in xenotransplanted animals without rise in toxicity.
Conclusion: In summary, we propose a very powerful new combination therapy for glioma.
