Huo Ku-Geng, D'Arcangelo Elisa, Tsao Ming-Sound
University Health Network and Princess Margaret Cancer Centre, Toronto, Canada.
Transl Lung Cancer Res. 2020 Oct;9(5):2214-2232. doi: 10.21037/tlcr-20-154.
Lung cancer accounts for most cancer-related deaths worldwide and has an overall 5-year survival rate of ~15%. Cell lines have played important roles in the study of cancer biology and potential therapeutic targets, as well as pre-clinical testing of novel drugs. However, most experimental therapies that have cleared preclinical testing using established cell lines have failed phase III clinical trials. This suggests that such models may not adequately recapitulate patient tumor biology and clinical outcome predictions. Here, we discuss and compare different pre-clinical lung cancer models, including established cell lines, patient-derived cell lines, xenografts and organoids, summarize the methodology for generating these models, and review their relative advantages and limitations in different oncologic research applications. We further discuss additional gaps in patient-derived pre-clinical models to better recapitulate tumor biology and improve their clinical predictive power.
肺癌是全球癌症相关死亡的主要原因,总体5年生存率约为15%。细胞系在癌症生物学和潜在治疗靶点的研究以及新药的临床前测试中发挥了重要作用。然而,大多数使用已建立的细胞系通过临床前测试的实验性疗法在III期临床试验中失败了。这表明此类模型可能无法充分重现患者肿瘤生物学和临床结果预测。在此,我们讨论并比较不同的临床前肺癌模型,包括已建立的细胞系、患者来源的细胞系、异种移植模型和类器官,总结生成这些模型的方法,并回顾它们在不同肿瘤学研究应用中的相对优势和局限性。我们还将进一步讨论患者来源的临床前模型中存在的其他差距,以更好地重现肿瘤生物学并提高其临床预测能力。