Navigating the clinical development landscape for oncolytic viruses and other cancer therapeutics: No shortcuts on the road to approval

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• 作者：Caroline J. Breitbach ; Tony Reid ; James Burke ; John C. Bell ; David H. Kirn
• 关键词：Oncolytic virus ; Targeted therapy ; Clinical development
• 刊名：Cytokine and Growth Factor Reviews
• 出版年：2010
• 出版时间：April-June 2010
• 年：2010
• 卷：21
• 期：2-3
• 页码：85-89
• 全文大小：239 K

文摘

Chemotherapy remains a common mode of anticancer treatment even though in most cancer indications the therapeutic approach is not effective and ultimately associated with the onset of chemoresistance. A better understanding of genetic differences in tumors ushered in the era of targeted therapy which has revolutionized the treatment of certain cancer types. However, generally targeted therapies are only cytostatic and a proportion of the patient population may be non-responsive to targeted therapy due to mutations of other genes in the same pathway (e.g. ras mutations in patients with colorectal cancer treated with EGFR targeted therapy). Therefore, there exists a need for a radically new approach to cancer therapy. Oncolytic viruses (OVs) possess many properties of an ideal cancer therapeutic. OVs are cytotoxic and target cancers via multiple mechanisms of action while at the same time exploiting validated genetic pathways known to be dysregulated in many cancers. Indeed, promising safety and efficacy data has emerged from Phase 1 and Phase 2 trials with diverse OVs (e.g. JX-594, a targeted oncolytic poxvirus). Though the field has lagged behind with pivotal, randomized Phase 3 trials, these are currently being initiated for a number of OVs. In addition, the field must ensure a continued clinical development of newly developed OVs; a strategy for the clinical development of novel cancer therapeutics is outlined.