Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
Genes (Basel). 2024 Sep 11;15(9):1193. doi: 10.3390/genes15091193.
Oncolytic viruses (OVs) are promising cancer immunotherapy agents that stimulate anti-tumor immunity through the preferential infection and killing of tumor cells. OVs are currently under limited clinical usage, due in part to their restricted efficacy as monotherapies. Current efforts for enhancement of the therapeutic potency of OVs involve their combination with other therapy modalities, aiming at the concomitant exploitation of complementary tumor weaknesses. In this context, microtubule-targeting agents (MTAs) pose as an enticing option, as they perturb microtubule dynamics and function, induce cell-cycle arrest, and cause mitotic cell death. MTAs induce therapeutic benefit through cancer-cell-autonomous and non-cell-autonomous mechanisms and are a main component of the standard of care for different malignancies. However, off-target effects and acquired resistance involving distinct cellular and molecular mechanisms may limit the overall efficacy of MTA-based therapy. When combined, OVs and MTAs may enhance therapeutic efficacy through increases in OV infection and immunogenic cell death and a decreased probability of acquired resistance. In this review, we introduce OVs and MTAs, describe molecular features of their activity in cancer cells, and discuss studies and clinical trials in which the combination has been tested.
溶瘤病毒（OVs）是一种很有前途的癌症免疫治疗药物，通过优先感染和杀死肿瘤细胞来刺激抗肿瘤免疫。OVs 的临床应用目前受到限制，部分原因是它们作为单一疗法的疗效有限。目前，增强 OVs 的治疗效力的努力包括将其与其他治疗方式结合，旨在同时利用互补的肿瘤弱点。在这种情况下，微管靶向剂（MTAs）是一个诱人的选择，因为它们扰乱微管动力学和功能，诱导细胞周期停滞，并导致有丝分裂细胞死亡。MTAs 通过癌细胞自主和非细胞自主机制诱导治疗益处，是不同恶性肿瘤标准治疗的主要组成部分。然而，涉及不同细胞和分子机制的脱靶效应和获得性耐药可能会限制基于 MTA 的治疗的总体疗效。当 OVs 和 MTAs 联合使用时，可能会通过增加 OV 感染和免疫原性细胞死亡以及降低获得性耐药的可能性来提高治疗效果。在这篇综述中，我们介绍了 OVs 和 MTAs，描述了它们在癌细胞中的活性的分子特征，并讨论了已经测试过这种联合治疗的研究和临床试验。
