Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400 019, India.
J Med Chem. 2020 Dec 24;63(24):15279-15307. doi: 10.1021/acs.jmedchem.0c01336. Epub 2020 Dec 16.
Cancer stem cells (CSCs), a subpopulation of cancer cells endowed with self-renewal, tumorigenicity, pluripotency, chemoresistance, differentiation, invasive ability, and plasticity, reside in specialized tumor niches and are responsible for tumor maintenance, metastasis, therapy resistance, and tumor relapse. The new-age "hierarchical or CSC" model of tumor heterogeneity is based on the concept of eradicating CSCs to prevent tumor relapse and therapy resistance. Small-molecular entities and biologics acting on various stemness signaling pathways, surface markers, efflux transporters, or components of complex tumor microenvironment are under intense investigation as potential anti-CSC agents. In addition, smart nanotherapeutic tools have proved their utility in achieving CSC targeting. Several CSC inhibitors in clinical development have shown promise, either as mono- or combination therapy, in refractory and difficult-to-treat cancers. Clinical investigations with CSC marker follow-up as a measure of clinical efficacy are needed to turn the "hype" into the "hope" these new-age oncology therapeutics have to offer.
癌症干细胞（CSC）是一类具有自我更新、肿瘤发生、多能性、耐药性、分化、侵袭能力和可塑性的肿瘤细胞亚群，存在于特定的肿瘤微环境中，负责肿瘤的维持、转移、治疗抵抗和肿瘤复发。基于根除 CSC 以预防肿瘤复发和治疗抵抗的概念，新型的“分层或 CSC”肿瘤异质性模型应运而生。作用于各种干性信号通路、表面标志物、外排转运体或复杂肿瘤微环境成分的小分子实体和生物制剂正作为潜在的抗 CSC 药物受到广泛研究。此外，智能纳米治疗工具已被证明可用于实现 CSC 靶向。几种处于临床开发阶段的 CSC 抑制剂作为单药或联合治疗，在难治性和治疗困难的癌症中显示出了希望。需要进行以 CSC 标志物随访作为临床疗效评估措施的临床研究，才能将这些新型肿瘤治疗药物的“炒作”转化为“希望”。
