Terzis A Jorge A, Niclou Simone P, Rajcevic Uros, Danzeisen Claude, Bjerkvig Rolf
National Department of Neurosurgery, Hospital Center Luxembourg, 4 Rue Barblé, L-1210, Luxembourg.
Expert Opin Biol Ther. 2006 Aug;6(8):739-49. doi: 10.1517/14712598.6.8.739.
Malignant gliomas, including the most devastating type, glioblastoma multiforme (GBM), are characterised by their local growth and aggressive infiltration of the normal brain. GBMs result in a profound disability, leading to death in almost all cases. There has been little improvement in outcome despite intensive clinical and laboratory research during recent decades. Interestingly, many researchers have been successful in treating GBM models in animals, but the success has been limited when new treatment principles have been translated into the clinic. One reason for this failure is the lack of appropriate animal models that reflect the behaviour of human GBMs. Therapeutic progress has also been hindered by the limited delivery of effective therapeutic compounds to an extremely heterogenic tumour cell population. This article discusses the present use and limitations of preclinical animal models to study glioma growth and progression. In addition, it focuses on the potential use of cell-based therapies for the treatment of GBMs. This includes aspects of gene therapy, stem cell therapy and immunotherapy. Several of these treatment modalities use the principle of transplanting cells or compounds that either directly or indirectly show therapeutic efficacy. Many of these principles depend on an increased biological knowledge of gliomas. The development of new therapeutic principles based on such knowledge may finally provide glioma patients with an improved survival.
恶性胶质瘤,包括最具破坏性的多形性胶质母细胞瘤(GBM),其特征在于局部生长以及对正常脑组织的侵袭性浸润。GBM会导致严重残疾,几乎在所有病例中都会导致死亡。尽管近几十年来进行了深入的临床和实验室研究,但治疗效果几乎没有改善。有趣的是,许多研究人员在治疗动物GBM模型方面取得了成功,但当新的治疗原则应用于临床时,成功却很有限。这种失败的一个原因是缺乏能够反映人类GBM行为的合适动物模型。有效治疗化合物向极其异质性的肿瘤细胞群体的有限递送也阻碍了治疗进展。本文讨论了临床前动物模型在研究胶质瘤生长和进展方面的当前应用及局限性。此外,它还关注基于细胞的疗法在治疗GBM方面的潜在应用。这包括基因治疗、干细胞治疗和免疫治疗等方面。这些治疗方式中有几种采用了移植细胞或化合物的原则,这些细胞或化合物直接或间接显示出治疗效果。其中许多原则依赖于对胶质瘤生物学知识的增加。基于此类知识开发新的治疗原则最终可能会提高胶质瘤患者的生存率。