Dept. of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Dept. of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Biochim Biophys Acta Rev Cancer. 2021 Aug;1876(1):188552. doi: 10.1016/j.bbcan.2021.188552. Epub 2021 Apr 21.
Small cell lung cancer (SCLC), a smoking-related highly aggressive neuroendocrine cancer, is characterized by rapid cell proliferation, early metastatic dissemination, and early relapse due to chemoresistance to first-line platinum-doublet chemotherapy. Genomically, SCLC tumors show nearly universal loss of TP53 and RB1 tumor suppressor genes, while gene expression signature classifies them into 4 distinct subgroups based on the expression patterns of lineage transcription factors - ASCL1/ASH1, NEUROD1, YAP-1, and POU2F3. Due to the lack of targetable molecular alterations and clinically useful diagnostic, prognostic and predictive biomarker, there is insignificant progress in the therapeutic management of SCLC patients. Numerous studies have shown a significant involvement of non-coding RNAs in the regulation of cell proliferation, invasion and migration, apoptosis, metastasis, and chemoresistance in various human cancers. In this review, we comprehensively discuss the role of microRNAs (miRNAs) in regulating the aforementioned biological process in SCLC. For this, we searched the scientific literature and selected studies that have evaluated the role of miRNAs in the disease pathogenesis or as a cancer biomarker in SCLC. Our review suggests that several miRNAs are involved in the pathogenesis of SCLC mainly by regulating cell proliferation, metastasis, and chemoresistance. Few studies have also demonstrated the clinical utility of miRNAs in monitoring response to chemotherapy as well as in predicting survival outcomes. However, more in-depth mechanistic studies utilizing in vivo models and multicentric studies with larger patient cohorts are needed before the applications of miRNAs as therapeutic targets or as biomarkers are translated from the laboratory into clinics.
小细胞肺癌（SCLC）是一种与吸烟有关的高度侵袭性神经内分泌癌，其特征为细胞增殖迅速、早期转移扩散以及对一线含铂双联化疗的耐药导致早期复发。从基因组学角度来看，SCLC 肿瘤几乎普遍丧失 TP53 和 RB1 肿瘤抑制基因，而基因表达谱根据谱系转录因子（ASCL1/ASH1、NEUROD1、YAP-1 和 POU2F3）的表达模式将其分为 4 个不同亚组。由于缺乏可靶向的分子改变以及临床上有用的诊断、预后和预测生物标志物，SCLC 患者的治疗管理进展甚微。大量研究表明，非编码 RNA 在各种人类癌症中对细胞增殖、侵袭和迁移、细胞凋亡、转移和耐药性的调控中具有重要作用。在这篇综述中，我们全面讨论了 microRNAs（miRNAs）在调节 SCLC 中上述生物学过程中的作用。为此，我们搜索了科学文献，并选择了评估 miRNAs 在疾病发病机制或作为 SCLC 癌症生物标志物中的作用的研究。我们的综述表明，几种 miRNAs 主要通过调节细胞增殖、转移和耐药性参与 SCLC 的发病机制。少数研究还证明了 miRNAs 在监测化疗反应以及预测生存结果方面的临床应用价值。然而，在 miRNA 作为治疗靶点或生物标志物从实验室转化为临床应用之前，还需要利用体内模型进行更深入的机制研究以及开展包含更大患者队列的多中心研究。
