Tumor-Targeted Macromolecular Drug Delivery Based on the Enhanced Permeability and Retention Effect in Solid Tumor


Cancer remains the first or second main cause of death in developed countries. In the world, 7.6 million people died of cancer in 2005 [1]. However, the cure for advanced cancer in major cancers has not improved in the past 50 years, although chemotherapy is supposed to be a last resort, if not all [2,3]. One of the recent successful stories in cancer chemotherapy is imatinib (Gleevec®), a drug for chronic myeloid leukemia (CML) which is an inhibitor of BCR/ABL tyrosine kinase, a product of oncogene. Imatinib shows a remarkable therapeutic effect against CML while a natural course of life span of CML patients is about 5 years. However, upon blastic period when the leukemic cell growth becomes exponential, majority of patients developed drug resistance within 6 months. Therefore, one can conclude that imatinib contributes only 10% prolongation of the life span.


Chronic Myeloid Leukemia Evans Blue Chronic Myeloid Leukemia Patient Vascular Endothelial Cell Growth Factor Blood Flow Volume 



Authors thank Ms Daruwalla J and Prof. Christophi C, Department of Surgery, Austin Health Hospital, University of Melbourne, Australia, for supplying the SEM pictures of blood capillaries used in Fig. 2A–F. Authors are indebted to all collaborators (to H. Maeda) for their painstaking assistance or support.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Innoventive Collaborative Organization, Kumamoto UniversityKumamotoJapan
  2. 2.BioDynamics Research Laboratory, Kumamoto University, Innoventive Collaborative Organization, Cooperative Research LaboratoryKumamotoJapan
  3. 3.Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo UniversityKumamotoJapan

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