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在非小细胞肺癌(NSCLC)中联合使用 YAP/TAZ 和 PD-L1 免疫检查点抑制剂靶向治疗。

Targeting YAP/TAZ in Combination with PD-L1 Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer (NSCLC).

机构信息

First University Department of Respiratory Medicine, "Sotiria" Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

出版信息

Cells. 2023 Mar 10;12(6):871. doi: 10.3390/cells12060871.

Abstract

The survival of non-small cell lung cancer (NSCLC) patients has improved in the last decade as a result of introducing new therapeutics, such as immune checkpoint inhibitors, in the clinic. Still, some NSCLC patients do not benefit from these therapies due to intrinsic resistance or the development of acquired resistance and their malignant disease progresses. Further research on the molecular underpinnings of NSCLC pathobiology is required in order to discover clinically relevant molecular targets that regulate tumor immunity and to develop reasonable therapeutic combinations that will promote the efficacy of immune checkpoint inhibitors. Yes-associated Protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), the final effectors of the Hippo signaling transduction pathway, are emerging as key players in NSCLC development and progression. Herein, we overview studies that have investigated the oncogenic role of YAP/TAZ in NSCLC, focusing on immune evasion, and highlight the therapeutic potential of combining YAP/TAZ inhibitory agents with immune checkpoint inhibitors for the management of NSCLC patients.

摘要

在过去的十年中,由于在临床上引入了新的治疗方法,如免疫检查点抑制剂,非小细胞肺癌 (NSCLC) 患者的生存率得到了提高。然而,由于内在耐药或获得性耐药的发展,一些 NSCLC 患者并未从这些治疗中获益,并且他们的恶性疾病进展。为了发现调节肿瘤免疫的临床相关分子靶点,并制定合理的治疗联合方案以提高免疫检查点抑制剂的疗效,需要进一步研究 NSCLC 病理生物学的分子基础。Yes 相关蛋白 (YAP) 和 PDZ 结合基序转录共激活因子 (TAZ) 是 Hippo 信号转导通路的最终效应物,它们正在成为 NSCLC 发生和发展的关键因素。本文综述了研究 YAP/TAZ 在 NSCLC 中的致癌作用的研究,重点关注免疫逃逸,并强调了 YAP/TAZ 抑制性药物与免疫检查点抑制剂联合用于 NSCLC 患者管理的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b652/10047112/10f8af447bba/cells-12-00871-g001.jpg

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