Frequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable " patient tumor's phenocopy" that represents molecular and functional heterogeneity of GBMs.
Bibliographical noteFunding Information:
This study was supported by a grant of the Korea Healthcare technology R&D project, Ministry for Health & Welfare Affairs, Republic of Korea (A092255), and by a Global Frontier Project grant (NRF-2012M3A6A-2010-0029781, 0029785) and the WCU project (R3-2008-000-10103-0) of the National Research Foundation funded by the Ministry of Education, Science and Technology of Korea. We thank Soonmyung Paik (Samsung Cancer Research Institute) for valuable scientific suggestions and Stephanie Sunny Ahn for help with illustrations. As a scientific resource for GBM, our GBM models would be distributed upon requests.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)