摘要
多形性胶质母细胞瘤是常见的原发性脑肿瘤,表现出胶质瘤细胞的生长和糖代谢的失衡。最近的研究发现,多种途径和下游基因参与异常调节的代谢途径以显示肿瘤及其进展,这对与重要的系统性和免疫抑制有关的胶质母细胞瘤患者至关重要。此外,免疫微环境被认为是产生有效的抗肿瘤免疫反应的主要障碍。因此,通过高度个性化的方式对病人特异的肿瘤抗原的鉴定,并与其他的治疗方法如靶向肿瘤代谢癌基因成瘾的分子药物和强效的宿主免疫调节剂的有效结合,可以为胶质母细胞瘤提供更有效的靶向治疗策略。这篇综述里,我们旨在强调对葡萄糖的摄取和增殖、细胞迁移的最新发现,我们扩展调查和更全面的检测对胶质母细胞瘤的葡萄糖代谢的不同方面,如戊糖磷酸途径(PPP)及其酶、遗传学和表观遗传学的代谢调控和关键的代谢调节剂,更重要的是,肿瘤细胞诱导的葡萄糖剥夺抑制T细胞糖酵解和免疫原性功能。此外,该综述将关注如何发现未来的有效治疗胶质母细胞瘤的药物靶点,来调控肿瘤和T细胞生长的糖代谢,并面临在肿瘤免疫微环境的代谢领域的挑战。
关键词: 胶质母细胞瘤,糖代谢,免疫抑制,治疗,肿瘤微环境。
Current Cancer Drug Targets
Title:Novel Strategies to Discover Effective Drug Targets in Metabolic and Immune Therapy for Glioblastoma
Volume: 17 Issue: 1
Author(s): Gang Wang, Xing-Li Fu, Jun-Jie Wang, Rui Guan, Xiang-Jun Tang
Affiliation:
关键词: 胶质母细胞瘤,糖代谢,免疫抑制,治疗,肿瘤微环境。
摘要: Glioblastoma multiforme is a common primary brain tumor, which exhibits an imbalance between glioma cell growth and glucose metabolism. Recent discoveries have found that the multiple pathways and downstream genes involved in the dysregulated metabolic pathway allow tumor to manifest and progress, which is critical to patients with glioblastoma associated with significant systemic and immunosuppression. Moreover, immune microenvironment is considered a major obstacle to generating an effective antitumor immune response. Therefore, identification of patient-specific tumor antigens through highly personalized approach, and effective combination with other therapeutic modalities such as molecular agents targeting tumor metabolic oncogene addiction and potent host immune modulators, may provide targets for more effective therapeutic strategies for glioblastoma. In this review, we aim to highlight the most recent findings regarding glucose uptake and proliferation, cell mobility and to expand our investigations and more comprehensively examine different aspects of glucose metabolism in glioblastoma, such as pentose phosphate pathway (PPP) and its enzymes, metabolic modulation of genetics and epigenetics and key metabolic regulators, importantly, tumor cell-induced glucose deprivation inhibits T-cell glycolysis and immunogenic functions. Furthermore, this review will concentrate on how to discover effective drug targets to regulate glucose metabolism in tumor and T cell growth for future glioblastoma therapies, and the challenges faced by the field of metabolism in tumor immune microenviroment.
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Cite this article as:
Gang Wang, Xing-Li Fu, Jun-Jie Wang, Rui Guan, Xiang-Jun Tang , Novel Strategies to Discover Effective Drug Targets in Metabolic and Immune Therapy for Glioblastoma, Current Cancer Drug Targets 2017; 17 (1) . https://dx.doi.org/10.2174/1568009616666160512145436
DOI https://dx.doi.org/10.2174/1568009616666160512145436 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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