Abstract:
In this chapter, we have made an attempt to elucidate the relevance of hedgehog signaling pathway in tumorigenesis. Here, we have described different types of hedgehog signaling (canonical and non-canonical) with emphasis on the different mechanisms (mutation-driven, autocrine, paracrine and reverse paracrine) it adopts during tumorigenesis. We have discussed the role of hedgehog signaling in regulating cell proliferation, invasion and epithelial-to-mesenchymal transition in both local and advanced cancer types, as reported in different studies based on preclinical and clinical models. We have specifically addressed the role of hedgehog signaling in aggressive neuroendocrine tumors as well. We have also elaborated on the studies showing therapeutic relevance of the inhibitors of hedgehog signaling in cancer. Evidence of the crosstalk of hedgehog signaling components with other signaling pathways and treatment resistance due to tumor heterogeneity have also been briefly discussed. Together, we have tried to put forward a compilation of the studies on therapeutic potential of hedgehog signaling in various cancers, specifically aggressive tumor types with a perspective into what is lacking and demands further investigation.
摘要:
在这一章中,我们已经尝试阐明hedgehog信号通路在肿瘤发生中的相关性。这里,我们已经描述了不同类型的刺猬信号(规范和非规范),重点是不同的机制(突变驱动,自分泌,旁分泌和反向旁分泌)在肿瘤发生过程中采用。我们已经讨论了hedgehog信号在调节细胞增殖中的作用,局部和晚期癌症类型的侵袭和上皮-间质转化,正如基于临床前和临床模型的不同研究所报道的那样。我们还专门讨论了hedgehog信号在侵袭性神经内分泌肿瘤中的作用。我们还详细阐述了显示hedgehog信号抑制剂在癌症中的治疗相关性的研究。hedgehog信号成分与其他信号通路的串扰以及由于肿瘤异质性引起的治疗抗性的证据也已被简要讨论。一起,我们试图提出一种关于刺猬信号在各种癌症中的治疗潜力的研究汇编,特别是侵袭性肿瘤类型,对缺乏的肿瘤有一个视角,需要进一步研究。