c-Jun N-terminal kinase (JNK) signalling regulates both cancer cell apoptosis and survival. Emerging evidence show that JNK promoted tumour progression is involved in various cancers, that include human pancreatic-, lung-, and breast cancer. The pro-survival JNK oncoprotein functions in a cell context- and cell type-specific manner to affect signal pathways that modulate tumour initiation, proliferation, and migration. JNK is therefore considered a potential oncogenic target for cancer therapy. Currently, designing effective and specific JNK inhibitors is an active area in the cancer treatment. Some ATP-competitive inhibitors of JNK, such as SP600125 and AS601245, are widely used in vitro; however, this type of inhibitor lacks specificity as they indiscriminately inhibit phosphorylation of all JNK substrates. Moreover, JNK has at least three isoforms with different functions in cancer development and identifying specific selective inhibitors is crucial for the development of targeted therapy in cancer. Some selective inhibitors of JNK are identified; however, their clinical studies in cancer are relatively less conducted. In this review, we first summarised the function of JNK signalling in cancer progression; there is a focus on the discussion of the novel selective JNK inhibitors as potential targeting therapy in cancer. Finally, we have offered a future perspective of the selective JNK inhibitors in the context of cancer therapies. We hope this review will help to further understand the role of JNK in cancer progression and provide insight into the design of novel selective JNK inhibitors in cancer treatment.

中文翻译：

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JNK信号传导的选择性抑制剂：潜在的靶向治疗癌症。

c-Jun N末端激酶（JNK）信号调节癌细胞凋亡和生存。新兴证据表明，JNK促进的肿瘤进展与多种癌症有关，包括人类胰腺癌，肺癌和乳腺癌。存活前JNK癌蛋白以细胞背景和细胞类型特异性方式起作用，以影响调节肿瘤起始，增殖和迁移的信号途径。因此，JNK被认为是癌症治疗的潜在致癌靶标。当前，设计有效和特异性的JNK抑制剂是癌症治疗中的活跃领域。JNK的某些具有ATP竞争性的抑制剂，例如SP600125和AS601245，已在体外得到广泛使用。然而，这种抑制剂缺乏特异性，因为它们不加选择地抑制所有JNK底物的磷酸化。此外，JNK具有至少三种在癌症发展中具有不同功能的同工型，鉴定特异性选择性抑制剂对于癌症靶向治疗的发展至关重要。确定了一些JNK的选择性抑制剂。然而，他们在癌症方面的临床研究相对较少。在这篇综述中，我们首先总结了JNK信号传导在癌症进展中的功能。有一种新型的选择性JNK抑制剂作为潜在的靶向治疗癌症的讨论的重点。最后，我们提供了在癌症治疗中选择性JNK抑制剂的未来前景。我们希望这篇综述将有助于进一步了解JNK在癌症进展中的作用，并为新型选择性JNK抑制剂在癌症治疗中的设计提供见识。