Birnboim-Perach Racheli, Benhar Itai
Department of Molecular Microbiology and Biotechnology, The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
Cancer Biology Research Center, Tel Aviv University, Tel-Aviv 69978, Israel.
Int J Biol Sci. 2024 Jul 15;20(10):3911-3922. doi: 10.7150/ijbs.93697. eCollection 2024.
Immune checkpoint inhibitors (ICIs) have heralded a new era in immunotherapy, representing a pivotal breakthrough in cancer treatment. Their impact is profound, with ICIs standing as some of the most prescribed anticancer therapies today. Notably, their ability to induce long-term remission even after treatment cessation provides genuine hope for achieving durable cures. However, despite these strides, challenges persist in the landscape of oncology, including resistance phenomena, immune-related adverse events, and suboptimal response rates. In response to these challenges, combination therapy emerges as a promising approach, poised to enhance treatment outcomes and address limitations inherent to single-agent ICI therapy. By synergistically targeting multiple pathways, combination therapy holds the potential to augment therapeutic efficacy while mitigating toxicity and impeding the emergence of resistance mechanisms. Understanding the intricacies underlying resistance development and adverse events is paramount in devising novel and refined combination strategies. A timeline showing FDA approvals of ICIs combination is shown in . This review aims to provide a comprehensive and up-to-date examples of different combined therapy strategies that can be used to overcome various challenges regarding ICI treatment. Through the exploration of innovative therapeutic combinations, we aim to provide clinicians and researchers with actionable knowledge to optimize patient outcomes and propel the field of immuno-oncology forward.
免疫检查点抑制剂(ICIs)开创了免疫治疗的新时代,代表了癌症治疗的一项关键突破。它们的影响意义深远,ICIs是当今处方量最多的一些抗癌疗法。值得注意的是,即使在停止治疗后,它们诱导长期缓解的能力也为实现持久治愈带来了真正的希望。然而,尽管取得了这些进展,肿瘤学领域仍存在挑战,包括耐药现象、免疫相关不良事件和次优反应率。为应对这些挑战,联合疗法成为一种有前景的方法,有望提高治疗效果并解决单药ICI疗法固有的局限性。通过协同靶向多种途径,联合疗法有可能增强治疗效果,同时减轻毒性并阻止耐药机制的出现。了解耐药性发展和不良事件背后的复杂机制对于设计新颖和精细的联合策略至关重要。图中展示了FDA批准ICIs联合疗法的时间表。本综述旨在提供不同联合治疗策略的全面且最新的实例,这些策略可用于克服ICI治疗方面的各种挑战。通过探索创新的治疗组合,我们旨在为临床医生和研究人员提供可操作的知识,以优化患者治疗效果并推动免疫肿瘤学领域向前发展。