Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.
Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
Cancer Metastasis Rev. 2024 Sep;43(3):889-918. doi: 10.1007/s10555-024-10174-x. Epub 2024 Feb 27.
Atezolizumab (TECENTRIQ®) and nivolumab (OPDIVO®) are both immunotherapeutic indications targeting programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 (PD-1), respectively. These inhibitors hold promise as therapies for triple-negative breast cancer (TNBC) and hepatocellular carcinoma (HCC) and have demonstrated encouraging results in reducing the progression and spread of tumors. However, due to their adverse effects and low response rates, the US Food and Drug Administration (FDA) has withdrawn the approval of atezolizumab in TNBC and nivolumab in HCC treatment. The withdrawals of atezolizumab and nivolumab have raised concerns regarding their effectiveness and the ability to predict treatment responses. Therefore, the current study aims to investigate the immunotherapy withdrawal of PD-1/PD-L1 inhibitors, specifically atezolizumab for TNBC and nivolumab for HCC. This study will examine both the structural and clinical aspects. This review provides detailed insights into the structure of the PD-1 receptor and its ligands, the interactions between PD-1 and PD-L1, and their interactions with the withdrawn antibodies (atezolizumab and nivolumab) as well as PD-1 and PD-L1 modifications. In addition, this review further assesses these antibodies in the context of TNBC and HCC. It seeks to elucidate the factors that contribute to diverse responses to PD-1/PD-L1 therapy in different types of cancer and propose approaches for predicting responses, mitigating the potential risks linked to therapy withdrawals, and optimizing patient outcomes. By better understanding the mechanisms underlying responses to PD-1/PD-L1 therapy and developing strategies to predict these responses, it is possible to create more efficient treatments for TNBC and HCC.
阿替利珠单抗(TECENTRIQ®)和纳武利尤单抗(OPDIVO®)分别是针对程序性死亡配体 1(PD-L1)和程序性死亡 1(PD-1)的免疫治疗药物。这些抑制剂有望成为三阴性乳腺癌(TNBC)和肝细胞癌(HCC)的治疗方法,已证明可减少肿瘤的进展和扩散。然而,由于其不良反应和低反应率,美国食品和药物管理局(FDA)已撤回了阿替利珠单抗治疗 TNBC 和纳武利尤单抗治疗 HCC 的批准。阿替利珠单抗和纳武利尤单抗的撤市引起了人们对其疗效和预测治疗反应能力的关注。因此,本研究旨在探讨 PD-1/PD-L1 抑制剂的免疫治疗撤市情况,特别是针对 TNBC 的阿替利珠单抗和针对 HCC 的纳武利尤单抗。本研究将从结构和临床两个方面进行探讨。本综述详细介绍了 PD-1 受体及其配体的结构、PD-1 与 PD-L1 的相互作用以及它们与撤市抗体(阿替利珠单抗和纳武利尤单抗)以及 PD-1 和 PD-L1 修饰物的相互作用。此外,本综述还进一步评估了这些抗体在 TNBC 和 HCC 中的应用。本综述旨在阐明导致不同类型癌症对 PD-1/PD-L1 治疗反应不同的因素,并提出预测反应、减轻与治疗撤市相关的潜在风险以及优化患者结局的方法。通过更好地了解 PD-1/PD-L1 治疗反应的机制并制定预测这些反应的策略,有可能为 TNBC 和 HCC 创造更有效的治疗方法。