Department of Biochemistry and Molecular Biology, Omaha, NE 68198, USA.
VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.
Int J Mol Sci. 2021 Apr 30;22(9):4765. doi: 10.3390/ijms22094765.
Despite significant improvements in clinical management, pancreatic cancer (PC) remains one of the deadliest cancer types, as it is prone to late detection with extreme metastatic properties. The recent findings that pancreatic cancer stem cells (PaCSCs) contribute to the tumorigenesis, progression, and chemoresistance have offered significant insight into the cancer malignancy and development of precise therapies. However, the heterogeneity of cancer and signaling pathways that regulate PC have posed limitations in the effective targeting of the PaCSCs. In this regard, the role for K-RAS, TP53, Transforming Growth Factor-β, hedgehog, Wnt and Notch and other signaling pathways in PC progression is well documented. In this review, we discuss the role of PaCSCs, the underlying molecular and signaling pathways that help promote pancreatic cancer development and metastasis with a specific focus on the regulation of PaCSCs. We also discuss the therapeutic approaches that target different PaCSCs, intricate mechanisms, and therapeutic opportunities to eliminate heterogeneous PaCSCs populations in pancreatic cancer.
尽管临床管理有了显著的进步，但胰腺癌（PC）仍然是致命癌症类型之一，因为它容易被晚期发现且具有极强的转移性。最近的研究发现，胰腺癌细胞干细胞（PaCSCs）有助于肿瘤发生、进展和化疗耐药性，这为癌症恶性程度和精确治疗的发展提供了重要的见解。然而，癌症的异质性和调节 PC 的信号通路在有效靶向 PaCSCs 方面带来了限制。在这方面，K-RAS、TP53、转化生长因子-β、 hedgehog、Wnt 和 Notch 等信号通路在 PC 进展中的作用已有相关记载。在这篇综述中，我们讨论了 PaCSCs 的作用，以及有助于促进胰腺癌发展和转移的潜在分子和信号通路，特别关注 PaCSCs 的调节。我们还讨论了针对不同 PaCSCs 的治疗方法、复杂机制以及消除胰腺癌中异质 PaCSCs 群体的治疗机会。
