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肺癌干细胞标志物作为治疗靶点:信号通路与治疗的最新进展

英文原题:Lung Cancer Stem Cell Markers as Therapeutic Targets: An Update on Signaling Pathways and Therapies.

PubMed 2022/05/26(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

研究概要

癌症干细胞是一群相对较小的自我更新的癌细胞,最初是从急性髓系白血病中分离出来的。

中文摘要

肿瘤干细胞是一小群具有自我更新能力的癌细胞,最初从急性髓系白血病中分离出来。这些细胞在肿瘤转移、复发和治疗耐药中可能发挥关键作用。肿瘤干细胞理论可能适用于肺癌,并可解释传统治疗的低效和最终复发。然而,由于肿瘤干细胞的准确性尚不明确且生物学功能难以捉摸,一些研究人员对该理论仍持谨慎态度。尽管争议持续存在,肿瘤干细胞仍在被研究中,其生物标志物也正在被发现,以应用于癌症诊断、靶向治疗和预后预测。潜在的肺癌干细胞标志物主要包括表面生物标志物,如 CD44、CD133、上皮细胞黏附分子和 ATP 结合盒亚家族 G 成员 2,以及细胞内生物标志物,如乙醛脱氢酶、性别决定区 Y 框 2、NANOG 和八聚体结合转录因子 4。这些标志物具有不同的结构和功能,但与肿瘤细胞的干性潜能和不可控增殖密切相关。Notch、Hedgehog 和 Wnt 等主要信号通路的异常激活,可能与某些肺癌干细胞标志物的表达和调控相关,从而导致肺癌干细胞的维持、化疗耐药和癌症促进。针对肺癌干细胞标志物的治疗,包括抗体药物、纳米颗粒药物、CAR-T 细胞治疗,以及其他天然或合成特异性抑制剂,可能为对常规肺癌治疗耐药的患者提供新的希望。本综述提供了关于肺癌干细胞标志物的全面且更新的数据,涉及其结构、功能、信号通路以及有前景的治疗靶点方法,旨在阐明肺癌的潜在新疗法。

展开英文摘要原文

Cancer stem cells, a relatively small group of self-renewing cancer cells, were first isolated from acute myeloid leukemia. These cells can play a crucial role in tumor metastasis, relapse, and therapy resistance. The cancer stem cell theory may be applied to lung cancer and explain the inefficiency of traditional treatments and eventual recurrence. However, because of the unclear accuracy and illusive biological function of cancer stem cells, some researchers remain cautious about this theory. Despite the ongoing controversy, cancer stem cells are still being investigated, and their biomarkers are being discovered for application in cancer diagnosis, targeted therapy, and prognosis prediction. Potential lung cancer stem cell markers mainly include surface biomarkers such as CD44, CD133, epithelial cell adhesion molecule, and ATP-binding cassette subfamily G member 2, along with intracellular biomarkers such as aldehyde dehydrogenase, sex-determining region Y-box 2, NANOG, and octamer-binding transcription factor 4. These markers have different structures and functions but are closely associated with the stem potential and uncontrollable proliferation of tumor cells. The aberrant activation of major signaling pathways, such as Notch, Hedgehog, and Wnt, may be associated with the expression and regulation of certain lung cancer stem cell markers, thus leading to lung cancer stem cell maintenance, chemotherapy resistance, and cancer promotion. Treatments targeting lung cancer stem cell markers, including antibody drugs, nanoparticle drugs, chimeric antigen receptor T-cell therapy, and other natural or synthetic specific inhibitors, may provide new hope for patients who are resistant to conventional lung cancer therapies. This review provides comprehensive and updated data on lung cancer stem cell markers with regard to their structures, functions, signaling pathways, and promising therapeutic target approaches, aiming to elucidate potential new therapies for lung cancer.

论文信息

作者
Zheng Y、Wang L、Yin L、Yao Z、Tong R、Xue J、Lu Y
单位
Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.China
文献类型
综述
期刊
Frontiers in oncology2022
原文标识
PubMed 35719973 · DOI 10.3389/fonc.2022.873994