Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy.

Linda S Steelman, Timothy Fitzgerald, Kvin Lertpiriyapong, Lucio Cocco, Matilde Y Follo, Alberto M Martelli, Luca M Neri, Sandra Marmiroli, Massimo Libra, Saverio Candido, Ferdinando Nicoletti, Aurora Scalisi, Concettina Fenga, Lyudmyla Drobot, Dariusz Rakus, Agnieszka Gizak, Piotr Laidler, Joanna Dulinska-Litewka, Joerg Basecke, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Giuseppe Montalto, Melchiorre Cervello, Michelle Milella, Agustino Tafuri, Zoya Demidenko, Stephen L Abrams, James A McCubrey

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.