Butowski Nicholas
Prog Neurol Surg. 2018;32:66-78. doi: 10.1159/000469681. Epub 2018 Jul 10.
Multiple alterations in the expression levels of genes or proteins have been identified in gliomas, including activation of oncogenes and silencing of tumor suppressor genes. Illuminating these molecular mechanisms of tumorigenesis and treatment resistance is necessary for the development of new therapies. With the promise of better effectiveness and less toxicity, the emphasis in drug development has moved from cytotoxic, non-specific chemotherapies to molecular targeted agents. However, despite progress in other areas of oncology, targeted therapy success stories in cases of brain tumors remain all but absent. Nonetheless, experiences from previous clinical trials suggest that a small number of unselected patients may benefit from such treatment. An increasing knowledge about related factors and prospective enrichment strategies now shape research and clinical trial design in neuro-oncology and may lead to improved outcomes after molecular targeted therapies of gliomas.
在胶质瘤中已发现基因或蛋白质表达水平的多种改变,包括癌基因的激活和肿瘤抑制基因的沉默。阐明这些肿瘤发生和治疗耐药的分子机制对于开发新疗法至关重要。由于有望获得更好的疗效和更低的毒性,药物开发的重点已从细胞毒性、非特异性化疗转向分子靶向药物。然而,尽管肿瘤学其他领域取得了进展,但脑肿瘤病例中的靶向治疗成功案例仍然几乎没有。尽管如此,以往临床试验的经验表明,少数未经选择的患者可能从这种治疗中获益。目前,对相关因素和前瞻性富集策略的认识不断增加,这正在塑造神经肿瘤学的研究和临床试验设计,并可能在胶质瘤的分子靶向治疗后带来更好的结果。