Targeting IL4/IL4R for the treatment of epithelial cancer metastasis.
Targeting IL4/IL4R for the treatment of epithelial cancer metastasis.
复制标题
DOI：
10.1007/s10585-015-9747-9
复制
发表时间：
2015-12
影响因子：
4
通讯作者：
Fingleton B
中科院分区：
文献类型：
--
作者：
Bankaitis KV;Fingleton B
虽然在治疗原发上皮性肿瘤方面取得了进展，但转移性肿瘤在很大程度上仍然是无法治愈的，仍然占所有癌症相关死亡的85%-90%。白介素4(IL4)是一种Th2细胞因子，IL4/IL4受体(IL4R)相互作用在免疫系统中具有明确的作用。然而，IL4受体在许多上皮性肿瘤中过度表达，可能成为转移肿瘤治疗的一个有前途的靶点。IL4/IL4R信号轴是上皮性癌细胞转移表型的强启动子，包括增强的迁移、侵袭、存活和增殖。IL4诱导的谷氨酰胺代谢也在一定程度上支持了促进乳腺癌生长的作用，我们已经证明IL4也能够诱导乳腺癌细胞的葡萄糖代谢。重要的是，FDA批准的几种用于哮喘患者的药物可以抑制IL4/IL4R信号轴。然而，这些批准的药物既抑制免疫细胞上发现的I型IL4受体，也抑制主要由包括上皮性癌细胞在内的一些非造血细胞表达的II型IL4受体。本文综述了针对IL4、IL4R或IL4/IL4R信号转导的现有治疗方法，以及在考虑对肿瘤微环境中免疫细胞的影响的同时，指导创造特异性抑制II型IL4R的新疗法的最新发现。其中一些疗法目前正在对癌症患者进行临床试验，可能会被用于治疗转移性疾病。
While progress has been made in treating primary epithelial tumors, metastatic tumors remain largely incurable and still account for 85–90% of all cancer-related deaths. Interleukin-4 (IL4), a Th2 cytokine, and the IL4/IL4 receptor (IL4R) interaction have well defined roles in the immune system. Yet, IL4 receptors are over-expressed by many epithelial cancers and could be a promising target for metastatic tumor therapy. The IL4/IL4R signaling axis is a strong promoter of pro-metastatic phenotypes in epithelial cancer cells including enhanced migration, invasion, survival, and proliferation. The promotion of breast cancer growth specifically is also supported in part by IL4-induced glutamine metabolism, and we have shown that IL4 is also capable of inducing glucose metabolism in breast cancer cells. Importantly, there are several types of FDA approved medications for use in asthma patients that inhibit the IL4/IL4R signaling axis. However, these approved medications inhibit both the type I IL4 receptor found on immune cells, and the type II IL4 receptor that is predominantly expressed by some non-hematopoietic cells including epithelial cancer cells. This article reviews existing therapies targeting IL4, IL4R, or IL4/IL4R signaling, and recent findings guiding the creation of novel therapies that specifically inhibit the type II IL4R, while taking into consideration effects on immune cells within the tumor microenvironment. Some of these therapies are currently in clinical trials for cancer patients, and may be exploitable for the treatment of metastatic disease.