There are more than 500 kinases in the human genome, many of which are oncogenic once constitutively activated. Fortunately, numerous hyperactive kinases are druggable, and several targeted small molecule kinase inhibitors have demonstrated impressive clinical benefits in cancer treatment. However, their often cytostatic rather than cytotoxic effect on cancer cells, and the development of resistance mechanisms, remain significant limitations to these targeted therapies. Oncolytic viruses are an emerging class of immunotherapeutic agents with a specific oncotropic nature and excellent safety profile, highlighting them as a promising alternative to conventional therapeutic modalities. Nonetheless, the clinical efficacy of oncolytic virotherapy is challenged by immunological and physical barriers that limit viral delivery, replication, and spread within tumours. Several of these barriers are often associated with oncogenic kinase activity and, in some cases, worsened by the action of oncolytic viruses on kinase signaling during infection. What if inhibiting these kinases could potentiate the cancer-lytic and anti-tumour immune stimulating properties of oncolytic virotherapies? This could represent a paradigm shift in the use of specific kinase inhibitors in the clinic and provide a novel therapeutic approach to the treatment of cancers. A phase III clinical trial combining the oncolytic Vaccinia virus Pexa-Vec with the kinase inhibitor Sorafenib was initiated. While this trial failed to show any benefits over Sorafenib monotherapy in patients with advanced liver cancer, several pre-clinical studies demonstrate that targeting kinases combined with oncolytic viruses have synergistic effects highlighting this strategy as a unique avenue to cancer therapy. Herein, we review the combinations of oncolytic viruses with kinase inhibitors reported in the literature and discuss the clinical opportunities that represent these pharmacoviral approaches.

人类基因组中有 500 多种激酶，其中许多一旦被组成性激活就具有致癌性。幸运的是，许多过度活跃的激酶是可成药的，并且几种靶向小分子激酶抑制剂已在癌症治疗中显示出令人印象深刻的临床益处。然而，它们对癌细胞的细胞抑制作用而不是细胞毒性作用，以及耐药机制的发展，仍然是这些靶向治疗的重大限制。溶瘤病毒是一类新兴的免疫治疗剂，具有特定的促瘤性质和出色的安全性，突出显示它们是传统治疗方式的有前途的替代品。尽管如此，溶瘤病毒疗法的临床疗效受到免疫和物理障碍的挑战，这些障碍限制了病毒的传递、复制、并在肿瘤内扩散。其中一些障碍通常与致癌激酶活性有关，并且在某些情况下，由于溶瘤病毒在感染期间对激酶信号传导的作用而恶化。如果抑制这些激酶可以增强溶瘤病毒疗法的抗癌和抗肿瘤免疫刺激特性呢？这可能代表了在临床中使用特定激酶抑制剂的范式转变，并为治疗癌症提供了一种新的治疗方法。开始了将溶瘤痘苗病毒 Pexa-Vec 与激酶抑制剂索拉非尼结合的 III 期临床试验。虽然该试验未能显示晚期肝癌患者比索拉非尼单药治疗有任何益处，几项临床前研究表明，靶向激酶与溶瘤病毒结合具有协同效应，突出了该策略作为癌症治疗的独特途径。在此，我们回顾了文献中报道的溶瘤病毒与激酶抑制剂的组合，并讨论了代表这些药物病毒方法的临床机会。