EGRF Targeting of Therapeutic Liposomes for Treating Gliobastoma

描述（由申请人提供）： 我们提出的研究将比较表皮生长因子受体（EGFR）靶向脂质体制剂拓扑替康（EGFR-LFT）与非靶向脂质体制剂拓扑替康（NT-LFT）治疗原位胶质母细胞瘤（GBM）异种移植物的疗效。作为本研究的一部分，我们还将探讨GBM EGFR状态（EGFR扩增vs.非扩增）和LFT给药途径（直接颅内给药vs.全身给药）作为影响LFT治疗疗效的因素。拓扑替康的脂质体制剂将作为单药以及与辐射组合进行测试。在请求的支持期结束时，该项目将解决LFT的全身递送是否是治疗脑肿瘤的可行策略，以及LFT的EGFR靶向递送是否应专门用于治疗EGFR扩增的肿瘤。更一般地说，该项目将解决是否EGFR靶向脂质体制剂化疗应进一步开发用于治疗GBM的临床实践。 公共卫生相关性： 本申请中提出的研究将确定是否可以利用高度恶性类型脑肿瘤中的分子特征来改善常用癌症治疗剂的递送和抗肿瘤效果。这些研究的结果将对改善大量抗癌药物的递送和功效具有重要意义。

DESCRIPTION (provided by applicant): The studies we are proposing will compare epidermal growth factor receptor (EGFR) targeted liposome- formulated topotecan (EGFR-LFT) vs. non-targeted liposome-formulated topotecan (NT-LFT) for efficacy in treating orthotopic glioblastoma (GBM) xenografts. As part of this research, we will also address GBM EGFR status (EGFR-amplified vs. non-amplified) and LFT route of delivery (direct intracranial administration vs. systemic administration) as factors that influence LFT therapeutic efficacy. Liposome formulations of topotecan will be tested as single agents as well as in combination with radiation. At the end of the requested period of support, this project will address whether systemic delivery of LFT is a viable strategy for treating brain tumors, and whether EGFR targeted delivery of LFT should be specifically used for treating tumors that have amplified EGFR. More generally, this project will address whether EGFR targeting of liposome-formulated chemotherapy should be further developed for use in clinical practice of treating GBM. PUBLIC HEALTH RELEVANCE: The studies proposed in this application will determine whether a molecular characteristic in a highly malignant type of brain tumor can be exploited for improving the delivery and anti-tumor effect of a commonly used cancer therapeutic. The results of these studies will have important implications for improving the delivery and efficacy of a large number of anti-cancer agents.