Reliance Life Sciences Pvt. Ltd., Dhirubhai Ambani Life Sciences Center, Thane Belapur Road, Rabale, Navi Mumbai, 400701, Maharashtra, India; Deakin University, School of Life and Environmental Sciences, Locked Bag 20000, Geelong, Victoria, 3220, Australia.
Deakin University, School of Life and Environmental Sciences, Locked Bag 20000, Geelong, Victoria, 3220, Australia.
Cytokine Growth Factor Rev. 2018 Jun;41:18-27. doi: 10.1016/j.cytogfr.2018.04.002. Epub 2018 Apr 7.
Epidermal growth factor receptor (EGFR) is a known target in cancer therapy and targeting the receptor has proven to be extremely successful in treating cancers that are dependent on EGFR signaling. To that effect, targeted therapies to EGFR such as Cetuximab, Panitumumab-monoclonal antibodies and Gefitinib, Erlotinib-tyrosine kinase inhibitors have had success in therapeutic scenarios. However, the development of resistance to these drugs makes it necessary to combine anti- EGFR therapies with other inhibitors, so that resistance can be overcome by the targeting of alternate signaling pathways. On the other hand, components of the inflammatory pathway, within and around a tumor, provide a conducive environment for tumor growth by supplying numerous cytokines and chemokines that foster carcinogenesis. Interleukin 6 (IL-6) is one such cytokine that is found to be associated with inflammation-driven cancers and which also plays a crucial role in acquired resistance to anti-EGFR drugs. The EGFR and IL-6 signaling pathways crosstalk in multiple ways, through various mediators and downstream signaling pathways driving resistance and hence co-targeting them has potential for future cancer treatments. Here we provide an overview on the crosstalk between the EGFR and IL-6 pathways, and discuss how co-targeting these two pathways could be a promising combination therapy of the future.
表皮生长因子受体 (EGFR) 是癌症治疗中的已知靶点，针对该受体的治疗已被证明在治疗依赖 EGFR 信号的癌症方面非常成功。为此，针对 EGFR 的靶向治疗方法，如西妥昔单抗、帕尼单抗单克隆抗体和吉非替尼、厄洛替尼酪氨酸激酶抑制剂，在治疗方案中取得了成功。然而，这些药物的耐药性发展使得有必要将抗 EGFR 疗法与其他抑制剂联合使用，以便通过靶向替代信号通路来克服耐药性。另一方面，肿瘤内和周围的炎症通路成分通过提供大量促进癌变的细胞因子和趋化因子，为肿瘤生长提供了有利的环境。白细胞介素 6 (IL-6) 就是这样一种与炎症驱动的癌症相关的细胞因子，它在获得性抗 EGFR 药物耐药性中也起着至关重要的作用。EGFR 和 IL-6 信号通路通过多种介质和下游信号通路以多种方式相互作用，从而驱动耐药性，因此针对这两条通路进行联合治疗可能是未来癌症治疗的一种有前途的联合疗法。在这里，我们概述了 EGFR 和 IL-6 通路之间的串扰，并讨论了联合靶向这两条通路如何成为未来有希望的联合治疗方法。
