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抗EBV相关鼻咽癌的靶向治疗新策略

2018年11月17日

编译：肿瘤资讯

来源：肿瘤资讯

抗EBV相关鼻咽癌的靶向治疗新策略

A．Dimitrios Colevas

教授

斯坦福大学医学中心

转移性鼻咽癌既往以常规化疗为主要治疗手段。以铂类药物、紫杉类、吉西他滨以及5FU及其类似物为代表的化疗药物显示出一定的临床疗效。然而，在靶向治疗和免疫治疗的时代，尚没有一种药物被广泛认可的治疗鼻咽癌的有效药物。由于绝大多数鼻咽癌都与EB病毒有关，以EB病毒的结构或免疫原性为靶点的靶向治疗，无论是大分子还是小分子，似乎都是合理的研究方向。然而，特异性靶向药物的研发目前还处于起步阶段，研制抗EBV特异性鼻咽癌治疗药物的道路上仍困难重重。

Dr. Colevas分享了两种抗EBV相关鼻咽癌的靶向治疗新方法。第一个是VK-2019。VK-2019是一种小分子，能够高度特异性地抑制EBNA-1的作用。他讲述了VK-2019的分子基础、临床前研究进展、分子选择策略及其在临床应用的情况。他还分享了针对EBV的新的细胞免疫疗法。

Emerging targeted strategies against EBV related NPC

Historically, widely disseminated nasopharyngeal cancer has been treated with conventional chemotherapeutics. In particular, platinum analogs, taxanes ,gemcitabine, as well as 5FU and its analogs have demonstrated clinically meaningful levels of activity. However, in the era of targeted therapy and immunotherapy there are no agents widely accepted as effective for the treatment of nasopharyngeal cancer. As the vast majority of nasopharynx cancer is Epstein Barr Virus(EBV) associated, it would seem logical that targeted therapy, either immunotherapy or small molecules, based upon molecular biological strategies which specifically target the machinery or immunogenicity of EBV would be most appropriate. However, development of specific targeted agents in this scenario is nascent, with no well- paved road of clinically successful anti-EBV specific treatments for NPC.

Dr. Colevas discuss two approaches to targeted therapy against EBV associated NPC. The first is a discussion of VK-2019, a small molecule designed to highly and specifically inhibit the actions of Epstein- Barr nuclear antigen 1 (EBNA-1). He discuss the molecular rationale, preclinical development, molecular selection strategy and status of VK-2019 in clinical development. He also discuss novel cellular based approaches to immunotherapy against NPC focusing on EBV beyond what is becoming more widely accepted checkpoint inhibitor monoclonal antibodies .