Molecular Motors and Glioma Dispersion

描述（由申请人提供）：恶性胶质瘤在正常大脑内扩散的能力最终使我们目前对这种肿瘤的所有治疗无效。抗血管生成药物进一步刺激了这种侵袭性倾向，这种药物已成为胶质瘤治疗的主流。不幸的是，旨在阻断这种侵袭性表型的治疗方法不能产生普遍或持久的反应，这强调了寻找针对这种肿瘤的脑分散的新方法的必要性。在我们之前的工作中，我们确定了分子运动非肌球蛋白II （NMMII）是胶质瘤侵袭装置的重要组成部分。在这项应用中，我们将在一组现实的、强大的胶质母细胞瘤临床前模型中研究NMMII在驱动胶质瘤侵袭中的作用，以及靶向NMMII阻断恶性胶质瘤侵袭表型的功效。这些转化研究的结果将与临床前模型中的联合治疗研究相结合，以确定NMMII抑制剂与抗血管生成和放射治疗之间的潜在协同作用。

DESCRIPTION (provided by applicant): The ability of malignant gliomas to disperse within normal brain ultimately renders ineffective all of our current therapies for this tumor. This invasive propensity is further stimulated by antiangiogenics, which have entered the mainstream of glioma therapeutics. Unfortunately, treatments designed to block this invasive phenotype do not produce universal or durable response, which underscores the need to find new ways of targeting brain dispersion by this tumor. In our prior work, we established that the molecular motor non-muscle myosin II (NMMII) is an essential component of the glioma invasion apparatus. In this application, we will examine the roles of NMMII in driving glioma invasion and the efficacy of targeting NMMII in blocking the invasive phenotype of malignant gliomas in a set of realistic and robust preclinical models of glioblastoma. Results from these translational studies will be combined with combination therapy studies in our pre-clinical models in order to identify potential synergy between NMMII inhibitors and anti-angiogenic and radiation therapy.