Mou Chenrui, Zou Shaotong, Ren Chao, Yi Zihan, Shi Jianlin
Department of Chest Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming 650118, China.
Kunming Medical University, Kunming 650032, China.
Zhongguo Fei Ai Za Zhi. 2025 May 20;28(5):363-370. doi: 10.3779/j.issn.1009-3419.2025.106.13.
Lung cancer is one of the most common cancers worldwide and is the leading cause of cancer deaths. Lung adenocarcinoma is the most common type of lung cancer. Due to the lack of effective biomarkers and therapeutic targets in the proliferation and metastasis of lung adenocarcinoma, the overall treatment of lung adenocarcinoma is not optimistic. Therefore, there is a need to find new ideas and methods for lung adenocarcinoma treatment. The 26S proteasome is a multiprotein complex responsible for degrading misfolded proteins and maintaining intracellular protein homeostasis. During the development of non-small cell lung cancer (NSCLC), the regulatory granule subunit of the 26S proteasome promotes the malignant progression of tumours by regulating tumour-associated proteins, immune cells, and related signalling pathways. The proteasome core particle is a key subunit for degrading proteins, and its inhibitors have shown promising anti-tumour effects when combined with conventional chemotherapeutic agents. However, limited by toxic side effects and tumour heterogeneity, targeted inhibitors against the 26S proteasome are still not widely used in NSCLC treatment. This article reviews the mechanism of action and related therapeutic research of 26S proteasome regulatory particle subunits and core particle subunits in NSCLC, and explores the potential of these inhibitors in clinical application. .
肺癌是全球最常见的癌症之一,也是癌症死亡的主要原因。肺腺癌是最常见的肺癌类型。由于肺腺癌增殖和转移中缺乏有效的生物标志物和治疗靶点,肺腺癌的整体治疗情况不容乐观。因此,需要寻找肺腺癌治疗的新思路和方法。26S蛋白酶体是一种多蛋白复合物,负责降解错误折叠的蛋白质并维持细胞内蛋白质稳态。在非小细胞肺癌(NSCLC)的发展过程中,26S蛋白酶体的调节颗粒亚基通过调节肿瘤相关蛋白、免疫细胞和相关信号通路促进肿瘤的恶性进展。蛋白酶体核心颗粒是蛋白质降解的关键亚基,其抑制剂与传统化疗药物联合使用时显示出有前景的抗肿瘤作用。然而,受毒副作用和肿瘤异质性的限制,针对26S蛋白酶体的靶向抑制剂在NSCLC治疗中仍未得到广泛应用。本文综述了26S蛋白酶体调节颗粒亚基和核心颗粒亚基在NSCLC中的作用机制及相关治疗研究,并探讨了这些抑制剂在临床应用中的潜力。