Department of Oncology, Eastern Health, University of Melbourne, Melbourne, Australia.
Cancer Rep (Hoboken). 2024 Oct;7(10):e70018. doi: 10.1002/cnr2.70018.
Small cell lung cancer (SCLC) harbours the most aggressive phenotype of all lung cancers to correlate with its bleak prognosis. The aggression of SCLC is partially attributable to its strong metastatic tendencies. The biological processes facilitating the metastasis in SCLC are still poorly understood and garnering a deeper understanding of these processes may enable the exploration of additional targets against this cancer hallmark in the treatment of SCLC.
This narrative review will discuss the proposed molecular mechanisms by which the cancer hallmark of activating invasion and metastasis is featured in SCLC through important steps of the metastatic pathway, and address the various molecular targets that may be considered for therapeutic intervention. The tumour immune microenvironment plays an important role in facilitating immunotherapy resistance, whilst the poor infiltration of natural killer cells in particular fosters a pro-metastatic environment in SCLC. SCLC vasculogenesis is achieved through VEGF expression and vascular mimicry, and epithelial-mesenchymal transition is facilitated by the expression of the transcriptional repressors of E-cadherin, the suppression of the Notch signalling pathway and tumour heterogeneity. Nuclear factor I/B, selectin and B1 integrin hold important roles in SCLC migration, whilst various molecular markers are expressed by SCLC to assist organ-specific homing during metastasis. The review will also discuss a recent article observing miR-1 mRNA upregulation as a potential therapeutic option in targeting the metastatic activity of SCLC.
Treatment of SCLC remains a clinical challenge due to its recalcitrant and aggressive nature. Amongst the many hallmarks used by SCLC to enable its aggressive behaviour, that of its ability to invade surrounding tissue and metastasise is particularly notable and understanding the molecular mechanisms in SCLC metastasis can identify therapeutic targets to attenuate SCLC aggression and improve mortality.
小细胞肺癌（SCLC）具有所有肺癌中最具侵袭性的表型，与其黯淡的预后相关。SCLC 的侵袭性部分归因于其强烈的转移倾向。促进 SCLC 转移的生物学过程仍知之甚少，深入了解这些过程可能会为治疗 SCLC 中这一癌症标志提供更多的治疗靶点。
本综述将讨论在 SCLC 中激活侵袭和转移的癌症标志的分子机制，通过转移途径的重要步骤，讨论各种可能被认为是治疗干预的分子靶点。肿瘤免疫微环境在促进免疫治疗耐药中起着重要作用，而自然杀伤细胞的渗透不良尤其促进了 SCLC 中的促转移环境。SCLC 的血管生成是通过 VEGF 表达和血管模拟实现的，上皮-间充质转化是通过 E-钙黏蛋白转录抑制因子的表达、Notch 信号通路的抑制和肿瘤异质性来促进的。核因子 I/B、选择素和 B1 整合素在 SCLC 迁移中具有重要作用，而 SCLC 表达的各种分子标记物则有助于转移过程中的器官特异性归巢。该综述还将讨论一篇最近的文章，观察到 miR-1 mRNA 的上调可能是一种有前途的治疗选择，用于靶向 SCLC 的转移活性。
由于 SCLC 的顽固性和侵袭性，治疗 SCLC 仍然是一个临床挑战。在 SCLC 用来使其具有侵袭性行为的许多特征中，其侵袭周围组织和转移的能力尤为显著，了解 SCLC 转移的分子机制可以确定治疗靶点，以减轻 SCLC 的侵袭性并提高死亡率。
