Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs.

IF 6.7
Oncolytic Virotherapy Pub Date : 2013-12-04 eCollection Date: 2013-01-01 DOI:10.2147/OV.S52601
Lynne Braidwood, Sheila V Graham, Alex Graham, Joe Conner
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引用次数: 6

Abstract

Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs) have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVex(GM-CSF)]), is almost complete, with extremely positive early results reported. Intuitively, therapeutically beneficial interactions between oHSV and chemotherapeutic and targeted therapeutic drugs would be limited as the virus requires actively dividing cells for maximum replication efficiency and most anticancer agents are cytotoxic or cytostatic. However, combinations of such agents display a range of responses, with antagonistic, additive, or, perhaps most surprisingly, synergistic enhancement of antitumor activity. When synergistic interactions in cancer cell killing are observed, chemotherapy dose reductions that achieve the same overall efficacy may be possible, resulting in a valuable reduction of adverse side effects. Therefore, the combination of an oHSV with "standard-of-care" drugs makes a logical and reasonable approach to improved therapy, and the addition of a targeted oncolytic therapy with "standard-of-care" drugs merits further investigation, both preclinically and in the clinic. Numerous publications report such studies of oncolytic HSV in combination with other drugs, and we review their findings here. Viral interactions with cellular hosts are complex and frequently involve intracellular signaling networks, thus creating diverse opportunities for synergistic or additive combinations with many anticancer drugs. We discuss potential mechanisms that may lead to synergistic interactions.

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溶瘤性疱疹病毒、化疗药物和其他抗癌药物。
溶瘤病毒正在成为一种治疗癌症的潜在新方法。它们是具有选择性复制能力的病毒,只在活跃分裂的肿瘤细胞中繁殖,而不在正常细胞中繁殖,结果通过裂解性感染破坏肿瘤细胞。迄今为止,至少有六种不同的溶瘤性单纯疱疹病毒(oHSVs)在世界范围内进行了临床试验,并证明了良好的安全性和有效性。首个oHSV关键性III期临床试验talimogene laherparepvec (T-Vec [OncoVex(GM-CSF)])已接近完成,早期结果报告非常积极。直观地说,oHSV与化疗药物和靶向治疗药物之间有益的相互作用将受到限制,因为病毒需要主动分裂细胞以获得最大的复制效率,而且大多数抗癌药物具有细胞毒性或细胞抑制剂。然而,这些药物的组合表现出一系列的反应,具有拮抗剂,添加剂,或者可能最令人惊讶的是,抗肿瘤活性的协同增强。当观察到癌细胞杀伤中的协同相互作用时,化疗剂量的减少可能达到相同的总体疗效,从而减少不良副作用。因此,将oHSV与“标准治疗”药物联合使用是一种合乎逻辑的、合理的改进治疗方法,在临床前和临床中,使用“标准治疗”药物进行靶向溶瘤治疗值得进一步研究。许多出版物报道了溶瘤性HSV与其他药物联合的研究,我们在这里回顾他们的发现。病毒与细胞宿主的相互作用是复杂的,并且经常涉及细胞内信号网络,因此为与许多抗癌药物的协同或加性组合创造了多种机会。我们讨论了可能导致协同相互作用的潜在机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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