Jackson Melanie, Hassiotou Foteini, Nowak Anna
Faculty of Science, School of Chemistry and Biochemistry and
Faculty of Science, School of Chemistry and Biochemistry and.
Carcinogenesis. 2015 Feb;36(2):177-85. doi: 10.1093/carcin/bgu243. Epub 2014 Dec 11.
Glioblastoma is the most common and most aggressive primary brain malignancy. The current initial standard of care consists of maximal safe surgical resection followed by radical radiotherapy and adjuvant temozolomide. Despite optimal therapy, median survival is ~15 months from diagnosis in molecularly unselected patients, and <6 months for patients with recurrent disease. Therefore, clinical treatments are currently palliative, not curative. Collectively, current knowledge suggests that the continued tumor growth and recurrence is in part due to the presence of glioma stem-like cells, which display self-renewal and tumorigenic potential. They differ from their more differentiated progeny, as they are more resistant to current treatments. Recurrent disease may be a consequence of the enhancement and/or gain of stem cell-like characteristics during disease progression, together with preferential death of more differentiated tumor cells during treatment, signifying that the cancer stem cell phenotype is a crucial therapeutic target. The limited knowledge of the characteristics of these cells and their response to current clinical treatments warrants intensive investigation with the aim to improve patient survival and/or develop a cure for this disease.
胶质母细胞瘤是最常见且最具侵袭性的原发性脑恶性肿瘤。目前的初始标准治疗方案包括最大限度的安全手术切除,随后进行根治性放疗和辅助替莫唑胺治疗。尽管采用了最佳治疗方法,但在未经分子筛选的患者中,从诊断开始计算的中位生存期约为15个月,而复发性疾病患者的中位生存期则小于6个月。因此,目前的临床治疗只是姑息性的,而非根治性的。总体而言,目前的认识表明,肿瘤的持续生长和复发部分归因于胶质瘤干细胞样细胞的存在,这些细胞具有自我更新和致瘤潜能。它们与其分化程度更高的子代细胞不同,因为它们对当前治疗更具抗性。复发性疾病可能是疾病进展过程中干细胞样特征增强和/或获得的结果,以及治疗期间分化程度更高的肿瘤细胞优先死亡的结果,这表明癌症干细胞表型是一个关键的治疗靶点。对这些细胞的特征及其对当前临床治疗反应的了解有限,因此有必要进行深入研究,以提高患者生存率和/或找到治愈这种疾病的方法。