Salgaller Michael L, Liau Linda M
Toucan Capital Corp, Bethesda, MD 20814, USA.
Rev Recent Clin Trials. 2006 Sep;1(3):265-81. doi: 10.2174/157488706778250140.
Glioblastoma, the most highly aggressive and lethal form of brain cancer, has been a particular challenge to treat in terms of improving a patient's quality of life and outcome. Each of the current treatment options is limited due to factors intrinsic to the tumor's biology and the special microenvironment of its location within the brain. Surgical resection is limited by the non-circumscribed borders that can be detected. Radiation therapy has to contend with neurotoxicity to adjacent normal tissues. Chemotherapy is constrained by the blood-brain barrier, which is a very real constraint of systemic therapy -- producing minimal benefit with substantial toxicity in order to administer therapeutic dosages. In part, such hurdles explain the reasons why survival has changed little over many decades of research in this field. The newest generation of treatments includes more effective cytotoxic agents, so-called targeted compounds, and biologics/immunotherapeutics. This article summarizes the preclinical proof-of-concept research and human studies involving some of the agents creating the most positive buzz in the medical community. The advantages and limitations of each are described.
胶质母细胞瘤是脑癌中最具侵袭性和致命性的形式,在改善患者生活质量和治疗结果方面一直是一项特殊挑战。由于肿瘤生物学的内在因素及其在脑内所处位置的特殊微环境,目前的每种治疗选择都存在局限性。手术切除受限于可检测到的边界不清晰。放射治疗必须应对对相邻正常组织的神经毒性。化疗受到血脑屏障的限制,这是全身治疗的一个非常现实的限制——为了给予治疗剂量,会产生极小的益处和大量的毒性。在一定程度上,这些障碍解释了为什么在该领域数十年的研究中生存率几乎没有变化。最新一代的治疗方法包括更有效的细胞毒性药物、所谓的靶向化合物以及生物制剂/免疫疗法。本文总结了涉及一些在医学界引起最积极反响的药物的临床前概念验证研究和人体研究。并描述了每种药物的优点和局限性。