The challenges and the promise of molecular targeted therapy in malignant gliomas.
The challenges and the promise of molecular targeted therapy in malignant gliomas.
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DOI：
10.1016/j.neo.2015.02.002
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发表时间：
2015-03
期刊：
影响因子：
4.8
通讯作者：
Chen, Juxiang
中科院分区：
文献类型：
--
作者：
Wang, Hongxiang;Xu, Tao;Jiang, Ying;Xu, Hanchong;Yan, Yong;Fu, Da;Chen, Juxiang
恶性神经胶质瘤是最常见的恶性原发性脑肿瘤，也是最具挑战性的癌症形式之一。尽管传统治疗取得了进展，但患者的结果仍然几乎都是致命的。这种不良的预后是由于治疗耐药和手术切除后肿瘤复发造成的。然而，在过去的十年中，分子靶向治疗有望改变恶性胶质瘤患者的治疗。在理解神经胶质瘤发生的分子病理学和恶性表型的维持方面取得的重大进展将为合理开发新的分子靶向治疗方案提供机会。最近，治疗策略集中于针对受体酪氨酸激酶/RAS/磷脂酰肌醇3激酶通路、促血管生成通路以及其他几个重要的细胞内信号网络（例如蛋白酶体和组蛋白脱乙酰酶）介导的促生长信号传导。然而，多种因素，例如改变的通路之间的串扰、瘤内分子异质性和神经胶质瘤干细胞（GSC）的治疗耐药性限制了单一药物的活性。我们正在努力深入研究神经胶质瘤的复杂分子生物学，开发针对 GSC 的新疗法，并确定生物标志物以对患者进行个体化分子靶向治疗分层。在此，我们回顾了与恶性胶质瘤病理学相关的分子改变，回顾了临床靶向试验的最新进展，并讨论了分子靶向治疗的挑战、争议和未来方向。
Malignant gliomas are the most common malignant primary brain tumors and one of the most challenging forms of cancers to treat. Despite advances in conventional treatment, the outcome for patients remains almost universally fatal. This poor prognosis is due to therapeutic resistance and tumor recurrence after surgical removal. However, over the past decade, molecular targeted therapy has held the promise of transforming the care of malignant glioma patients. Significant progress in understanding the molecular pathology of gliomagenesis and maintenance of the malignant phenotypes will open opportunities to rationally develop new molecular targeted therapy options. Recently, therapeutic strategies have focused on targeting pro-growth signaling mediated by receptor tyrosine kinase/RAS/phosphatidylinositol 3-kinase pathway, proangiogenic pathways, and several other vital intracellular signaling networks, such as proteasome and histone deacetylase. However, several factors such as cross-talk between the altered pathways, intratumoral molecular heterogeneity, and therapeutic resistance of glioma stem cells (GSCs) have limited the activity of single agents. Efforts are ongoing to study in depth the complex molecular biology of glioma, develop novel regimens targeting GSCs, and identify biomarkers to stratify patients with the individualized molecular targeted therapy. Here, we review the molecular alterations relevant to the pathology of malignant glioma, review current advances in clinical targeted trials, and discuss the challenges, controversies, and future directions of molecular targeted therapy.
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DOI：
10.1016/j.ijrobp.2012.10.008
发表时间：
2013-04-01
影响因子：
7
作者：
Chakravarti, Arnab;Wang, Meihua;Robins, H. Ian;Lautenschlaeger, Tim;Curran, Walter J.;Brachman, David G.;Schultz, Christopher J.;Choucair, Ali;Dolled-Filhart, Marisa;Christiansen, Jason;Gustavson, Mark;Molinaro, Annette;Mischel, Paul;Dicker, Adam P.;Bredel, Markus;Mehta, Minesh
通讯作者：
Mehta, Minesh
雷帕霉素在I期试验中针对复发性PTEN缺陷型胶质母细胞瘤患者的抗肿瘤活性。
影响因子：
15.8
作者：
Cloughesy, Tim F.;Yoshimoto, Koji;Nghiemphu, Phioanh;Brown, Kevin;Dang, Julie;Zhu, Shaojun;Hsueh, Teli;Chen, Yinan;Wang, Wei;Youngkin, David;Liau, Linda;Martin, Neil;Becker, Don;Bergsneider, Marvin;Lai, Albert;Green, Richard;Oglesby, Tom;Koleto, Michael;Trent, Jeff;Horvath, Steve;Mischel, Paul S.;Mellinghoff, Ingo K.;Sawyers, Charles L.
通讯作者：
Sawyers, Charles L.
在遗传学和组织学精确的脑干神经胶质瘤模型中，辐射和perifosine的临床前评估。
影响因子：
11.2
作者：
Becher OJ;Hambardzumyan D;Walker TR;Helmy K;Nazarian J;Albrecht S;Hiner RL;Gall S;Huse JT;Jabado N;MacDonald TJ;Holland EC
通讯作者：
Holland EC
影响因子：
3.9
作者：
Chaponis D;Barnes JW;Dellagatta JL;Kesari S;Fast E;Sauvageot C;Panagrahy D;Greene ER;Ramakrishna N;Wen PY;Kung AL;Stiles C;Kieran MW
通讯作者：
Kieran MW
影响因子：
5.3
作者：
Cabanas, Ricardo;Saurez, Giselle;Crombet Ramos, Tania
通讯作者：
Crombet Ramos, Tania