Inflammation is at the forefront of carcinogenesis, tumor progression and resistance to therapy. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling axis is a central pathway that mediates the cellular response to inflammation and contributes to carcinogenesis. The JAK/STAT pathway coordinates intercellular communication between tumor cells and their immune microenvironment, and JAK/STAT activation leads to the expression of a variety of proteins involved in cell proliferation, cell survival, stemness, self-renewal, evasion of immunosurveillance mechanisms and overall tumor progression. Activation of JAK/STAT signaling also mediates resistance to radiation therapy or cytotoxic agents and modulates tumor cell responses to molecularly targeted and immune modulating drugs. Despite extensive research focused on understanding its signaling mechanisms and downstream phenotypic and functional consequences in hematological disorders, the importance of JAK/STAT signaling in solid tumor initiation and progression has been underappreciated. We highlight the role of chronic inflammation in cancer, the epidemiological evidence for contribution of JAK/STAT to carcinogenesis, the current cancer prevention measures involving JAK/STAT inhibition and the impact of JAK/STAT signaling activity on cancer development, progression and treatment resistance. We also discuss recent therapeutic advances in targeting key factors within the JAK/STAT pathway with single agents and the use of these agents in combination with other targeted therapies and immune checkpoint inhibitors.

中文翻译：

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各行各业的 JAK/STAT：将炎症与癌症发展、肿瘤进展和治疗抗性联系起来。

炎症处于致癌、肿瘤进展和治疗抵抗的最前沿。Janus 激酶 (JAK)/信号转导和转录激活因子 (STAT) 信号轴是介导细胞对炎症的反应并促进致癌作用的中心通路。JAK/STAT 通路协调肿瘤细胞与其免疫微环境之间的细胞间通讯，JAK/STAT 激活导致多种参与细胞增殖、细胞存活、干性、自我更新、逃避免疫监视机制和整体的蛋白质的表达。肿瘤进展。JAK/STAT 信号的激活还介导对放射治疗或细胞毒剂的抗性，并调节肿瘤细胞对分子靶向和免疫调节药物的反应。尽管广泛的研究集中在了解其在血液疾病中的信号传导机制以及下游表型和功能后果，但 JAK/STAT 信号传导在实体瘤起始和进展中的重要性一直被低估。我们强调慢性炎症在癌症中的作用、JAK/STAT 对致癌作用的流行病学证据、当前涉及 JAK/STAT 抑制的癌症预防措施以及 JAK/STAT 信号活性对癌症发展、进展和治疗抵抗的影响。我们还讨论了用单一药物靶向 JAK/STAT 通路中关键因素的最新治疗进展，以及这些药物与其他靶向治疗和免疫检查点抑制剂联合使用的情况。