Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., NC10, Cleveland, OH, 44195, USA.
Departments of Pharmacology and Medicine (Hematology/Oncology), Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Target Oncol. 2017 Aug;12(4):387-399. doi: 10.1007/s11523-017-0508-3.
Advances in cancer research in the past have led to an evolving understanding of cancer pathogenesis and the development of novel drugs that significantly improve patient outcomes. However, many patients still encounter treatment resistance, recurrence, or metastasis and eventually die from progressing disease. Experimental evidence indicates that a subpopulation of cancer cells, called cancer stem cells (CSCs), possess "stemness" properties similar to normal stem cells, including self-renewal, differentiation, and proliferative potential. These stemness properties are lost during differentiation and are governed by pathways such as STAT3, NANOG, NOTCH, WNT, and HEDGEHOG, which are highly dysregulated in CSCs due to genetic and epigenetic changes. Promising results have been observed in preclinical models targeting these CSCs through the disruption of stemness pathways in combination with current treatment modalities. This has led to anti-CSC-based clinical trials in multiple stages of development. In this review, we discuss the role of CSCs and stemness pathways in cancer treatment and how they relate to clinical observations. Because CSCs and the stemness pathways governing them may explain the negative clinical outcomes observed during treatment, it is important for oncologists to understand how they contribute to cancer progression and how they may be targeted to improve patient outcomes.
过去癌症研究的进展导致人们对癌症发病机制的认识不断发展，并开发出了新型药物，这些药物显著改善了患者的预后。然而，许多患者仍然面临治疗耐药、复发或转移，并最终死于疾病进展。实验证据表明，癌细胞的一个亚群，称为癌症干细胞（CSCs），具有类似于正常干细胞的“干性”特性，包括自我更新、分化和增殖潜力。这些干性特性在分化过程中丢失，并受到 STAT3、NANOG、NOTCH、WNT 和 HEDGEHOG 等途径的调控，由于遗传和表观遗传的改变，CSCs 中的这些途径高度失调。通过破坏干性途径并与当前的治疗方式相结合，针对这些 CSCs 的临床前模型观察到了有希望的结果。这导致了基于抗 CSC 的临床试验进入多个开发阶段。在这篇综述中，我们讨论了 CSCs 和调控它们的干性途径在癌症治疗中的作用，以及它们与临床观察的关系。因为 CSCs 和调控它们的干性途径可能解释了在治疗过程中观察到的负面临床结果，因此肿瘤学家了解它们如何促进癌症进展以及如何针对它们以改善患者预后非常重要。
