Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), E-08003 Barcelona, Spain.
Int J Mol Sci. 2020 Mar 11;21(6):1913. doi: 10.3390/ijms21061913.
The p38 MAPK pathway is well known for its role in transducing stress signals from the environment. Many key players and regulatory mechanisms of this signaling cascade have been described to some extent. Nevertheless, p38 participates in a broad range of cellular activities, for many of which detailed molecular pictures are still lacking. Originally described as a tumor-suppressor kinase for its inhibitory role in RAS-dependent transformation, p38 can also function as a tumor promoter, as demonstrated by extensive experimental data. This finding has prompted the development of specific inhibitors that have been used in clinical trials to treat several human malignancies, although without much success to date. However, elucidating critical aspects of p38 biology, such as isoform-specific functions or its apparent dual nature during tumorigenesis, might open up new possibilities for therapy with unexpected potential. In this review, we provide an extensive description of the main biological functions of p38 and focus on recent studies that have addressed its role in cancer. Furthermore, we provide an updated overview of therapeutic strategies targeting p38 in cancer and promising alternatives currently being explored.
p38 MAPK 通路因其在传递环境应激信号方面的作用而广为人知。该信号级联的许多关键参与者和调节机制已经在一定程度上得到了描述。然而，p38 参与了广泛的细胞活动，其中许多活动的详细分子机制仍不清楚。最初被描述为一种肿瘤抑制激酶，因其在 RAS 依赖性转化中的抑制作用，p38 也可以作为肿瘤促进剂发挥作用，这一发现已被广泛的实验数据所证实。这一发现促使开发了特异性抑制剂，并在临床试验中用于治疗多种人类恶性肿瘤，但迄今为止并没有取得太大成功。然而，阐明 p38 生物学的关键方面，例如同工型特异性功能或其在肿瘤发生过程中的明显双重性质，可能为治疗提供新的可能性，并具有意想不到的潜力。在这篇综述中，我们对 p38 的主要生物学功能进行了广泛的描述，并重点介绍了最近研究其在癌症中的作用的研究。此外，我们还对靶向 p38 的癌症治疗策略进行了更新概述，并探讨了目前正在探索的有前途的替代方法。
