Research over decades has enabled us in developing a better understanding of the multifaceted and heterogeneous nature of cancer. High-throughput technologies have helped the researchers in unraveling of the underlying mechanisms which centrally regulate cancer onset, metastasis and drug resistance. Our rapidly expanding knowledge about signal transduction cascade has added another layer of complexity to already complicated nature of cancer. Deregulation of cell signaling pathways played a linchpin role in carcinogenesis and metastasis. Cucurbitacins have gained tremendous attention because of their remarkable pharmacological properties and considerable ability to mechanistically modulate myriad of cell signaling pathways in different cancers. In this review, we have attempted to provide a mechanistic and comprehensive analysis of regulation of oncogenic pathways by cucurbitacins in different cancers. We have partitioned this review into separate sections for exclusive analysis of each signaling pathway and critical assessment of the knowledge gaps. In this review, we will summarize most recent and landmark developments related to regulation of Wnt/β-catenin, JAK/STAT, mTOR, VEGFR, EGFR and Hippo pathway by cucurbitacins. Moreover, we will also address how cucurbitacins regulate DNA damage repair pathway and TRAIL-driven signaling in various cancers. However, there are still outstanding questions related to regulation of SHH/GLI, TGF/SMAD and Notch-driven pathway by cucurbitacins in different cancers. Future studies must converge on the analysis of full-fledge potential of cucurbitacins by in-depth analysis of these pathways and how these pathways can be therapeutically targeted by cucurbitacins.

数十年的研究使我们能够更好地了解癌症的多面性和异质性。高通量技术帮助研究人员揭示了集中调节癌症发病、转移和耐药性的潜在机制。我们关于信号转导级联的快速扩展知识为已经复杂的癌症性质增加了另一层复杂性。细胞信号通路的失调在癌变和转移中发挥了关键作用。葫芦素因其显着的药理特性和在不同癌症中机械调节无数细胞信号通路的强大能力而获得了极大的关注。在本次审查中，我们试图对葫芦素在不同癌症中对致癌途径的调节进行机械和全面的分析。我们已将这篇评论划分为单独的部分，以便对每个信号通路进行专门分析，并对知识差距进行批判性评估。在这篇综述中，我们将总结与葫芦素对 Wnt/β-catenin、JAK/STAT、mTOR、VEGFR、EGFR 和 Hippo 通路的调节相关的最新和具有里程碑意义的发展。此外，我们还将讨论葫芦素如何调节各种癌症中的 DNA 损伤修复途径和 TRAIL 驱动的信号传导。然而，葫芦素在不同癌症中对 SHH/GLI、TGF/SMAD 和 Notch 驱动通路的调控仍存在悬而未决的问题。