Supervisor: Professor XUE HONG, department of Basic Medicine And Clinical Pharmacy
STRATEGIES TO DELIVER ANTI-CANCER DRUGS TO BRAIN TUMORS
Abstract:
Malignant brain tumors are among the most challenging to treat and at the present there are no uniformly successful treatment strategies. Standard treatment regimens consist of maximal surgical resection followed by radiotherapy and chemotherapy. The limited survival advantage attributed to chemotherapy is partially due to low central nervous system (CNS) penetration of antineoplastic agents across the blood-brain barrier (BBB). Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties, increase specificity and bioavailability, improve shelf life, and reduce toxicity. Some nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain tumors. Vessels in tumors have abnormal architecture and are highly permeable; moreover, tumors also have poor lymphatic drainage, allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor microenvironment. Nanoparticles exploit this feature, known as the enhanced permeability and retention effect, to target solid tumors. Active targeting, surface modification of nanoparticles, is a way to decrease uptake in normal tissue and increase accumulation in a tumor, and it usually involves targeting surface membrane proteins that are upregulated in cancer cells. This review proposal is based on the study of literature and theories of previous studies.
Introduction:
According to the GLOBOCAN 2008, the worldwide cancer incidence of malignant brain tumors is 3.5 per 100000 people and about 650 people are diagnosed with malignant brain tumors every day. Brain tumors are divided into two groups: (1) primary, originating and residing within the brain and (2) secondary (metastatic), originating from a primary cancer outside the central nervous system and spreading into the brain. Metastatic tumors are more frequent than primary tumors in adult patients while primary ones are the most frequent solid tumors of childhood. The histological spectrum of brain tumors in children and adolescents differs from that in adults. Brain tumors severely threaten human health due to their fast development and poor prognosis. The most frequent primary brain cancer is Glioma, accounts for 29 percent of all primary brain and CNS tumors and 80 percent of malignant brain tumors. The median overall survival of patients with glioblastoma (GBM) is only 14 months after current multimodal treatment and aggressive surgical resection followed by concurrent or sequential radiotherapy and chemotherapies. The reason why poor prognosis and rapid recurrence are associated with this standard therapy is that the infiltrate growth of gliomas makes it difficult for the surgeon to completely remove pathologic or cancer infiltrated tissues without affecting normal brain functions. Furthermore, the failure is also ascribed to the side effects of radiotherapy and poor outcome of usual chemotherapy. For many years, researchers have endeavored to deliver therapeutic agents to the tumor region effectively and reduce unnecessary drug accumulation in normal brain and peripheral tissues. However, recent studies suggested that nanodrugs can over come the blood brain barrier (BBB), which is the biggest obstacle when it comes to treating brain tumors and the brain in general.
The Blood Brain Barrier (BBB):
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