靶向癌症中的 MAPK 信号通路：药物耐药性和敏感性的机制。

Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity.

机构信息

Systems Biology Ireland, School of Medicine, University College Dublin, Dublin 4, Ireland.

School of Biomolecular and Biomedical Science, University College Dublin, Dublin 4, Ireland.

出版信息

Int J Mol Sci. 2020 Feb 7;21(3):1102. doi: 10.3390/ijms21031102.

DOI:10.3390/ijms21031102

PMID:32046099

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7037308/

Abstract

Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Here, we focus on the role of MAPK pathways in modulating drug sensitivity and resistance in cancer. We briefly discuss new findings in the extracellular signaling-regulated kinase (ERK) pathway, but mainly focus on the mechanisms how stress activated MAPK pathways, such as p38 MAPK and the Jun N-terminal kinases (JNK), impact the response of cancer cells to chemotherapies and targeted therapies. In this context, we also discuss the role of metabolic and epigenetic aberrations and new therapeutic opportunities arising from these changes.

摘要

丝裂原活化蛋白激酶（MAPK）途径是普遍存在的信号转导途径，调节生命的各个方面，并且在疾病中经常发生改变。在这里，我们重点关注 MAPK 途径在调节癌症药物敏感性和耐药性中的作用。我们简要讨论细胞外信号调节激酶（ERK）途径中的新发现，但主要关注应激激活 MAPK 途径（如 p38 MAPK 和 Jun N-末端激酶（JNK））如何影响癌细胞对化疗和靶向治疗的反应的机制。在这方面，我们还讨论了代谢和表观遗传异常的作用，以及由此产生的新的治疗机会。