Department of Surgery, City of Hope Medical Center, Duarte, CA, USA.
Department of Hematology, City of Hope Medical Center, Duarte, CA, USA.
Cancer Gene Ther. 2023 Sep;30(9):1181-1189. doi: 10.1038/s41417-023-00622-1. Epub 2023 May 29.
Gastrointestinal cancers are a leading cause of cancer morbidity and mortality worldwide with 4.2 million new cases and 3.2 million deaths estimated in 2020. Despite the advances in primary and adjuvant therapies, patients still develop distant metastases and require novel therapies. Mitogen‑activated protein kinase (MAPK) cascades are crucial signaling pathways that regulate many cellular processes, including proliferation, differentiation, apoptosis, stress responses and cancer development. p38 Mitogen Activated Protein Kinases (p38 MAPKs) includes four isoforms: p38α (MAPK14), p38β (MAPK11), p38γ (MAPK12), and p38δ (MAPK13). p38 MAPK was first identified as a stress response protein kinase that phosphorylates different transcriptional factors. Dysregulation of p38 pathways, in particular p38γ, are associated with cancer development, metastasis, autophagy and tumor microenvironment. In this article, we provide an overview of p38 and p38γ with respect to gastrointestinal cancers. Furthermore, targeting p38γ is also discussed as a potential therapy for gastrointestinal cancers.
胃肠道癌症是全世界癌症发病率和死亡率的主要原因，据估计，2020 年全球新发病例 420 万例，死亡病例 320 万例。尽管原发性和辅助治疗取得了进展，但患者仍会发生远处转移，需要新的治疗方法。丝裂原活化蛋白激酶（MAPK）级联反应是调节许多细胞过程的关键信号通路，包括增殖、分化、凋亡、应激反应和癌症发生。p38 丝裂原活化蛋白激酶（p38 MAPK）包括四个同工型：p38α（MAPK14）、p38β（MAPK11）、p38γ（MAPK12）和 p38δ（MAPK13）。p38 MAPK 最初被鉴定为一种应激反应蛋白激酶，可磷酸化不同的转录因子。p38 通路的失调，特别是 p38γ 的失调，与癌症的发生、转移、自噬和肿瘤微环境有关。本文就 p38 和 p38γ 与胃肠道癌症的关系作一综述，并探讨靶向 p38γ 作为胃肠道癌症潜在治疗方法的可能性。
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