Study the biological factors for glial cell malignancy and development of brain drug delivery system

Malignant glioma is a severe brain tumor with a high recurrence rate and poor prognosis. The progression of glioma is a complex process, the low grade tumors evolve into fast growing and invasive high grade tumors under the influence of numerous factors associated with malignancy. For effective tumor progression, growth, invasion and metastasis, a continuous cross-talk between cancer cells and local/distant host environment is required. For glioma malignant progression and treatment, the outcome is not only related to the response of cancer cells, but also depending on the results of interaction with tumor microenvironments. Thus, study of these biological factors may provide clues for diagnosis/prognosis and treatment. In the past few years under the support of NHRI, we have established a bank of brain tumor clinical resources and data including tumor tissues and serum specimens, molecular imaging data, cultured primary tumor cells, patient derived xenograft models and brain tumor stem cells. For comprehensive study of the tumor progress mechanism and interaction with the microenvironment, we systematically collected clinical samples by both longitudinal level (low grade to high grade, primary tumor and recurrent tumors) and anatomic level (tumor mass, periphery tissue and distal normal tissues). In this study, selected biological factors will be further analyzed and studied for the correlation with our available clinical information. We will collaborate with cell biology experts from NHRI for studying the detailed tumor progression mechanisms. Our aim is to discover the potential diagnostic/prognostic/therapeutic targets that can be detected by current conventional examination including MRI or laboratory tests. The second part of this study is to develop therapeutic system for brain tumors. With the support from NHRI, we have used techniques based on nano-medicine and focused on ultrasound to develop a world-leading brain lesion drug delivery system. Due to the heterogeneous nature of malignant glioma, single chemotherapy may only be effective to some extent. Thus, multiple treatment strategy may be beneficial to brain tumor control. Here we will take the advantage of the properties of our multifunctional nano-drug carriers served as acoustic thermal therapy, neutron capture therapy and gene therapy agents. We will collaborate with NHRI experts for development of neutron capture therapy for brain tumors. The selected therapeutic targets from our part 1 study will also be used to develop our novel multifunctional nano-drug carriers. This is an extension of previous approved proposal. During the past two and half years, we had published several results, and performed the first-in-man clinical of neuronavigator guided focused ultrasound. We will keep working on our original proposal, and the extension part will be focused on 1. Using the state-of-art single cell analysis technique to investigate the characters and mechanism for malignant progression; 2. Developing new target drugs that can be applied to focused ultrasound brain drug delivery systems to promote its clinical applications. From study of the tumor progression molecular markers and development of the therapeutic systems, it will be promising for future brain tumor treatment and may improve the life quality of brain tumor patients.

Project ID:PG10801-0138
External Project ID:NHRI-EX108-10502NI