National Centre for Cell Science, Pune 411007, India.
National Centre for Cell Science, Pune 411007, India.
Cytokine. 2022 Sep;157:155968. doi: 10.1016/j.cyto.2022.155968. Epub 2022 Jul 21.
Tumor heterogeneity, in principle, reflects the variation among different cancer cell populations. It can be termed inter- or intra-tumoral heterogeneity, respectively, based on its occurrence in various tissues from diverse patients or within a single tumor. The intra-tumoral heterogeneity is one of the leading causes of cancer progression and treatment failure, with the cancer stem cells (CSCs) contributing immensely to the same. These niche cells, similar to normal stem cells, possess the characteristics of self-renewal and differentiation into multiple cell types. Moreover, CSCs contribute to tumor growth and surveillance by promoting recurrence, metastasis, and therapeutic resistance. Diverse factors, including intracellular signalling pathways and tumor microenvironment (TME), play a vital role in regulating these CSCs. Although a panel of markers is considered to identify the CSC pool in various cancers, further research is needed to discriminate cancer-specific CSC markers in those. CSCs have also been found to be promising therapeutic targets for cancer therapy. Several small molecules, natural compounds, antibodies, chimeric antigen receptor T (CAR-T) cells, and CAR-natural killer (CAR-NK) cells have emerged as therapeutic tools for specific targeting of CSCs. Interestingly, many of these are in clinical trials too. Despite being a much-explored avenue of research for years, and we have come to understand its nitty-gritty, there is still a tremendous gap in our knowledge concerning its precise genesis and regulation. Hence, a concrete understanding is needed to assess the CSC-TME link and how to target different cancer-specific CSCs by designing newer tools. In this review, we have summarized CSC, its causative, different pathways and factors regulating its growth, association with tumor heterogeneity, and last but not least, discussed many of the promising CSC-targeted therapies for combating cancer metastasis.
肿瘤异质性原则上反映了不同癌细胞群体之间的变异。根据其在不同患者的不同组织中或单个肿瘤内的发生情况，可分别将其称为肿瘤间或肿瘤内异质性。肿瘤内异质性是癌症进展和治疗失败的主要原因之一，其中癌症干细胞（CSC）对此贡献巨大。这些生态位细胞与正常干细胞相似，具有自我更新和分化为多种细胞类型的特征。此外，CSC 通过促进复发、转移和治疗耐药性，促进肿瘤生长和监测。包括细胞内信号通路和肿瘤微环境（TME）在内的多种因素在调节这些 CSC 中起着至关重要的作用。尽管有一组标记物被认为可以识别各种癌症中的 CSC 池，但仍需要进一步研究以区分这些癌症中的癌症特异性 CSC 标记物。CSC 也已被发现是癌症治疗的有前途的治疗靶点。几种小分子、天然化合物、抗体、嵌合抗原受体 T（CAR-T）细胞和嵌合抗原受体自然杀伤（CAR-NK）细胞已成为针对 CSC 的特异性靶向治疗工具。有趣的是，其中许多也正在临床试验中。尽管多年来一直是研究的热门领域，我们已经了解了其本质，但对于其确切的发生和调节，我们的知识仍然存在巨大差距。因此，需要具体了解 CSC-TME 之间的联系以及如何通过设计新的工具针对不同的癌症特异性 CSC。在这篇综述中，我们总结了 CSC、其病因、调节其生长的不同途径和因素、与肿瘤异质性的关联，最后但并非最不重要的是，讨论了许多有前途的针对 CSC 的癌症转移治疗方法。
