Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Guwahati, Sila Katamur, Halugurisuk P.O-Changsari, Kamrup, Assam, India-781101.
Institute of Pharmaceutical Research, GLA University, Mathura, U.P., India.
J Environ Pathol Toxicol Oncol. 2023;42(4):15-29. doi: 10.1615/JEnvironPatholToxicolOncol.2023045403.
According to the World Health Organization (WHO), cancer is the second-highest cause of mortality worldwide, killing nearly 9.6 million people annually. Despite the advances in diagnosis and treatment during the last couple of decades, it remains a serious concern due to the limitations of currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. In addition, many etiological factors such as environmental and genetic factors initiate the activation of the Janus kinase (JAK)-signal transducer and activator of the transcription (STAT) pathway. This aberrant activation of the JAK-STAT pathway has been reported in various disease states, including inflammatory conditions, hematologic malignancies, and cancer. For instance, many patients with myeloproliferative neoplasms carry the acquired gain-of-function JAK2 V617F somatic mutation. This knowledge has dramatically improved our understanding of pathogenesis and has facilitated the development of therapeutics capable of suppressing the constitutive activation of the JAK-STAT pathway. Our aim is not to be expansive but to highlight emerging ideas towards preventive therapy in a modern view of JAK-STAT inhibitors. A series of agents with different specificities against different members of the JAK family of proteins is currently undergoing evaluation in clinical trials. Here we give a summary of how JAK-STAT inhibitors function and a detailed review of current clinical drugs for managing cancer as a new therapeutic approach.
根据世界卫生组织（WHO）的数据，癌症是全球第二大死亡原因，每年导致近 960 万人死亡。尽管在过去几十年中诊断和治疗方面取得了进展，但由于目前可用的癌症管理策略存在局限性，癌症仍然是一个严重的问题。因此，需要替代策略来克服这些问题。此外，许多病因因素，如环境和遗传因素，会引发 Janus 激酶（JAK）-信号转导和转录激活因子（STAT）通路的激活。这种 JAK-STAT 通路的异常激活已在各种疾病状态中得到报道，包括炎症性疾病、血液恶性肿瘤和癌症。例如，许多骨髓增生性肿瘤患者携带获得性功能获得的 JAK2 V617F 体细胞突变。这一知识极大地提高了我们对发病机制的理解，并促进了能够抑制 JAK-STAT 通路组成性激活的治疗药物的发展。我们的目的不是广泛介绍，而是在现代 JAK-STAT 抑制剂的视角下，突出预防治疗的新观点。目前正在临床试验中评估一系列针对 JAK 家族蛋白不同成员具有不同特异性的药物。在这里，我们总结了 JAK-STAT 抑制剂的作用机制，并详细回顾了目前用于癌症治疗的临床药物，作为一种新的治疗方法。
