Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China.
Cell Death Dis. 2021 Sep 4;12(9):835. doi: 10.1038/s41419-021-04116-6.
Quiescence has been observed in stem cells (SCs), including adult SCs and cancer SCs (CSCs). Conventional chemotherapies mostly target proliferating cancer cells, while the quiescent state favors CSCs escape to chemotherapeutic drugs, leaving risks for tumor recurrence or metastasis. The tumor microenvironment (TME) provides various signals that maintain resident quiescent CSCs, protect them from immune surveillance, and facilitates their recurrence potential. Since the TME has the potential to support and initiate stem cell-like programs in cancer cells, targeting the TME components may prove to be a powerful modality for the treatment of chemotherapy resistance. In addition, an increasing number of studies have discovered that CSCs exhibit the potential of metabolic flexibility when metabolic substrates are limited, and display increased robustness in response to stress. Accompanied by chemotherapy that targets proliferative cancer cells, treatments that modulate CSC quiescence through the regulation of metabolic pathways also show promise. In this review, we focus on the roles of metabolic flexibility and the TME on CSCs quiescence and further discuss potential treatments of targeting CSCs and the TME to limit chemotherapy resistance.
静止状态在干细胞（SCs）中被观察到，包括成体干细胞和癌症干细胞（CSCs）。传统的化疗主要针对增殖的癌细胞，而静止状态有利于 CSCs 逃避化疗药物，从而增加肿瘤复发或转移的风险。肿瘤微环境（TME）提供了各种信号，维持着常驻静止 CSCs，并保护它们免受免疫监视，促进它们的复发潜力。由于 TME 有可能在癌细胞中支持和启动干细胞样程序，针对 TME 成分可能被证明是治疗化疗耐药的一种有效方式。此外，越来越多的研究发现，当代谢底物有限时，CSCs 表现出代谢灵活性的潜力，并在应对压力时表现出更强的稳健性。与针对增殖癌细胞的化疗相结合，通过调节代谢途径来调节 CSC 静止状态的治疗方法也显示出了希望。在这篇综述中，我们重点讨论了代谢灵活性和 TME 对 CSC 静止状态的作用，并进一步讨论了针对 CSC 和 TME 的潜在治疗方法，以限制化疗耐药性。
