Integrins and p53 pathways in glioblastoma resistance to temozolomide.
Integrins and p53 pathways in glioblastoma resistance to temozolomide.
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DOI：
10.3389/fonc.2012.00157
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发表时间：
2012
影响因子：
4.7
通讯作者：
Dontenwill M
中科院分区：
文献类型：
--
作者：
Martin S;Janouskova H;Dontenwill M
胶质母细胞瘤是最常见的恶性原发性脑肿瘤。手术切除、术后放疗加替莫唑胺（TMZ）伴随和辅助化疗是新诊断胶质母细胞瘤的标准治疗。在过去的十年中，已经努力破译基因组和核心途径的改变，以确定临床相关的胶质母细胞瘤亚型。在这些研究的基础上，通过更多的学术探索，发现了新的潜在治疗靶点，并开发了多种靶向药物。这样的分子应该有望克服胶质母细胞瘤对目前治疗的抵抗力。胶质母细胞瘤亚型的特征之一是细胞外基质/侵袭相关基因的富集。整合素是胶质瘤细胞迁移/侵袭和血管生成中重要的细胞粘附分子，是这些基因之一。整合素似乎是相关的治疗靶点和拮抗剂最近到达临床。虽然p53通路在胶质母细胞瘤中经常发生改变，但在关于p53状态对TMZ耐药性的临床相关影响的文献中可以发现相互矛盾的结果。在这里，我们将总结目前的知识（1）整合素的表达，（2）p53的状态，（3）整合素和p53之间的关系，以讨论他们的潜在影响胶质母细胞瘤耐药替莫唑胺。
Glioblastoma is the most common malignant primary brain tumor. Surgical resection, postoperative radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide (TMZ) is the standard of care for newly diagnosed glioblastoma. In the past decade, efforts have been made to decipher genomic and core pathway alterations to identify clinically relevant glioblastoma subtypes. Based on these studies and more academic explorations, new potential therapeutic targets were found and several targeting agents were developed. Such molecules should hopefully overcome the resistance of glioblastoma to the current therapy. One of the hallmarks of glioblastoma subtypes was the enrichment of extracellular matrix/invasion-related genes. Integrins, which are cell adhesion molecules important in glioma cell migration/invasion and angiogenesis were one of those genes. Integrins seem to be pertinent therapeutic targets and antagonists recently reached the clinic. Although the p53 pathway appears often altered in glioblastoma, conflicting results can be found in the literature about the clinically relevant impact of the p53 status in the resistance to TMZ. Here, we will summarize the current knowledge on (1) integrin expression, (2) p53 status, and (3) relationship between integrins and p53 to discuss their potential impact on the resistance of glioblastoma to temozolomide.