Steelman Linda S, Fitzgerald Timothy, Lertpiriyapong Kvin, Cocco Lucio, Follo Matilde Y, Martelli Alberto M, Neri Luca M, Marmiroli Sandra, Libra Massimo, Candido Saverio, Nicoletti Ferdinando, Scalisi Aurora, Fenga Concettina, Drobot Lyudmyla, Rakus Dariusz, Gizak Agnieszka, Laidler Piotr, Dulinska-Litewka Joanna, Basecke Joerg, Mijatovic Sanja, Maksimovic-Ivanic Danijela, Montalto Giuseppe, Cervello Melchiorre, Milella Michelle, Tafuri Agustino, Demidenko Zoya, Abrams Stephen L, McCubrey James A
Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Brody Building 5N98C, Greenville, NC 27858 USA.
Curr Pharm Des. 2016;22(16):2358-88. doi: 10.2174/1381612822666160304151011.
The roles of the epidermal growth factor receptor (EGFR) signaling pathway in various cancers including breast, bladder, brain, colorectal, esophageal, gastric, head and neck, hepatocellular, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and other cancers have been keenly investigated since the 1980's. While the receptors and many downstream signaling molecules have been identified and characterized, there is still much to learn about this pathway and how its deregulation can lead to cancer and how it may be differentially regulated in various cell types. Multiple inhibitors to EGFR family members have been developed and many are in clinical use. Current research often focuses on their roles and other associated pathways in cancer stem cells (CSCs), identifying sites where therapeutic resistance may develop and the mechanisms by which microRNAs (miRs) and other RNAs regulate this pathway. This review will focus on recent advances in these fields with a specific focus on breast cancer and breast CSCs. Relatively novel areas of investigation, such as treatments for other diseases (e.g., diabetes, metabolism, and intestinal parasites), have provided new information about therapeutic resistance and CSCs.
自20世纪80年代以来，表皮生长因子受体（EGFR）信号通路在包括乳腺癌、膀胱癌、脑癌、结直肠癌、食管癌、胃癌、头颈癌、肝细胞癌、肺癌、神经母细胞瘤、卵巢癌、胰腺癌、前列腺癌、肾癌及其他癌症在内的多种癌症中的作用一直受到密切研究。虽然已经鉴定并表征了该受体及许多下游信号分子，但关于这条信号通路、其失调如何导致癌症以及它在各种细胞类型中可能如何受到差异调节，仍有许多有待了解的地方。针对EGFR家族成员的多种抑制剂已被开发出来，其中许多正在临床应用中。当前的研究通常聚焦于它们在癌症干细胞（CSC）中的作用及其他相关信号通路，确定可能产生治疗抗性的位点以及微小RNA（miR）和其他RNA调节这条信号通路的机制。本综述将聚焦于这些领域的最新进展，特别关注乳腺癌和乳腺CSC。相对较新的研究领域，如针对其他疾病（如糖尿病、代谢和肠道寄生虫）的治疗，为治疗抗性和CSC提供了新信息。
