Molecular Motors and Glioma Dispersion

描述(申请人提供)：恶性胶质瘤在正常大脑中扩散的能力最终导致我们目前对这种肿瘤的所有治疗都无效。抗血管生成药物进一步刺激了这种侵袭倾向，抗血管生成药物已进入胶质瘤治疗的主流。不幸的是，旨在阻止这种侵袭性表型的治疗并没有产生普遍或持久的反应，这突显了寻找新的方法来靶向这种肿瘤的脑部分散的必要性。在我们之前的工作中，我们确定了分子马达非肌肉肌球蛋白II(NMMII)是胶质瘤侵袭机制的重要组成部分。在这一应用中，我们将在一组真实和强大的胶质母细胞瘤临床前模型中检测NMMII在推动胶质瘤侵袭中的作用以及靶向NMMII在阻断恶性胶质瘤侵袭表型方面的有效性。这些翻译研究的结果将与我们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.