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Pancreatic Cancer and Therapy: Role and Regulation of Cancer Stem Cells

期刊

出版社

MDPI
DOI: 10.3390/ijms22094765

关键词

MASTL; pancreatic cancer; chemoresistance

资金

  1. VA merit [BX002086, BX002761]
  2. NIH/NCI [CA250383, CA216746]
  3. Fred and Pamela Buffet Cancer Center - National Cancer Institute Cancer Center Support Grant [P30 CA036727, DK124095]

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Despite advancements in clinical management, pancreatic cancer remains deadly due to late detection and high metastatic properties. Pancreatic cancer stem cells have been found to play a crucial role in tumorigenesis, progression, and chemoresistance, but targeting them effectively remains a challenge due to cancer heterogeneity and complex signaling pathways regulating PC progression.
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-beta, 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.

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