Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Cancer Metastasis Rev. 2018 Sep;37(2-3):385-395. doi: 10.1007/s10555-018-9746-9.
Eicosanoids are bioactive lipids that play crucial roles in various pathophysiological conditions, including inflammation and cancer. They include both the COX-derived prostaglandins and the LOX-derived leukotrienes. Furthermore, the epidermal growth factor receptor (EGFR) pathways family of receptor tyrosine kinases also are known to play a central role in the tumorigenesis. Various antitumor modalities have been approved cancer treatments that target therapeutically the COX-2 and EGFR pathways; these include selective COX-2 inhibitors and EGFR monoclonal antibodies. Research has shown that the COX-2 and epidermal growth factor receptor pathways actively interact with each other in order to orchestrate carcinogenesis. This has been used to justify a targeted combinatorial approach aimed at these two pathways. Although combined therapies have been found to have a greater antitumor effect than the administration of single agent, this does not exempt them from the possible fatal cardiac effects that are associated with COX-2 inhibition. In this review, we delineate the contribution of HB-EGF, an important EGFR ligand, to the cardiac dysfunction related to decreased shedding of HB-EGF after COX-2/PGE2 inhibition. A better understanding of the molecular mechanisms underlying these cardiac side effects will make possible more effective regimens that use the dual-targeting approach.
类二十烷酸是生物活性脂质，在各种病理生理条件下发挥关键作用，包括炎症和癌症。它们包括 COX 衍生的前列腺素和 LOX 衍生的白三烯。此外，表皮生长因子受体 (EGFR) 途径家族的受体酪氨酸激酶也被认为在肿瘤发生中起核心作用。已经批准了各种抗肿瘤方式来治疗癌症，这些方式靶向治疗 COX-2 和 EGFR 途径；其中包括选择性 COX-2 抑制剂和 EGFR 单克隆抗体。研究表明，COX-2 和表皮生长因子受体途径相互积极作用，以协调致癌作用。这被用来证明针对这两个途径的靶向组合方法是合理的。尽管联合治疗已被发现比单一药物治疗具有更大的抗肿瘤作用，但这并不能免除它们与 COX-2 抑制相关的可能致命的心脏效应。在这篇综述中，我们描述了 HB-EGF（一种重要的 EGFR 配体）在 COX-2/PGE2 抑制后 HB-EGF 脱落减少相关的心脏功能障碍中的作用。更好地了解这些心脏副作用的分子机制将有可能制定更有效的方案，采用双重靶向方法。
