Study and Application of Glial Cell Specific Antigens in CNS

Malignant glioma is a common and severe primary brain tumor with a high recurrence rate and a poor prognosis. Surgical resection of solid tumor followed by chemo-/radio-therapy is the standard treatment for malignant brain tumor. However, systemic administered chemotherapeutic drugs have limited use because of their adverse systemic effects and poor blood–brain barrier (BBB) penetration. Furthermore, these treatments might kill the majority of tumor cells and induce temporary regression of gross tumor lesions but fail to prevent disease relapse and metastatic dissemination. Thus, development of an effective new therapeutic system against GBM is in urgent need. In our previous study, several potential brain tumor markers were identified and a prototype of tumor treatment system was established. The first aim of the study is using system biology tool to analysis these biomarkers. The second aim is to identify brain tumor stem cells. Among our candidate biomarkers, CD44 is recently considered as a cancer stem cell (CSC) marker. CSCs are tumorigenic even in only few populations; therapeutic strategy fail to target CSC may result in relapse and metastasis. Thus, we propose to develop a brain tumor therapeutic system, which not only kill the majority of cancer cells but also target on brain tumor stem cells. The surface marker (CD44) and nuclear markers (CD44, STAT3, cmyc, SOX2 and OCT4) will be used for phenotypic identification and enumeration of CSCs. And then, to develop therapies that target the CSC population, it will be important to find and validate intermediate end points that predict ultimate patient survival. The selected targets will be applied for preparation of intelligent nanoparticle drug carrier for CSC targeting and killing. The third aim is to develop a novel drug deliver system for brain tumor. For enhancement of drug delivery efficacy of antitumor agents, we combine focused ultrasound to transiently permeabilize the blood–brain barrier, and use magnetic targeting to enhance localization of magnetic nanoparticles. Molecular targeting probes for cancer cells and CSCs will be immobilized on the magnetic nanoparticle drug carriers for selective killing of brain tumor and CSCs. Such innovative applications of emerging technologies promise to provide more effective means of tumor treatment, with lower therapeutic doses and potentially fewer side effects and may prevent disease relapse and metastatic dissemination.

Project ID:PG10401-0080
External Project ID:NHRI-EX104-10004NI