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

Abstract

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.

Clinical and molecular insights into adenoid cystic carcinoma: Neural crest‐like stemness as a target

“…Importantly, existing data suggest that these CSCs hijack embryonic signaling, interconvert between different neurotrophic receptors, and benefit from cross talk between neurotrophic and other signaling pathways. Better understanding of these complex signaling interactions is essential for designing effective combination strategies that could take advantage of recently produced NOTCH, FGFR, Trk, and other RTK inhibitors to thwart acquired and intrinsic drug and radiation resistance …”

“…Better understanding of these complex signaling interactions is essential for designing effective combination strategies that could take advantage of recently produced NOTCH, FGFR, Trk, and other RTK inhibitors to thwart acquired and intrinsic drug and radiation resistance. 126,221,222 Epigenetic Targeting of Stemness in Adenoid Cystic Carcinoma…”

Knockdown of Musashi RNA Binding Proteins Decreases Radioresistance but Enhances Cell Motility and Invasion in Triple-Negative Breast Cancer

“…MSI knockdown downregulates EGFR, thus providing another potential mechanism to enhance radiosensitivity. EGFR also plays a key role for BCSC activity [47], demonstrating yet again that many of the aforementioned mechanisms are closely related.…”

Recent developments in nanomedicine for melanoma treatment

“…Target agents can identify and combine specifically with molecules that are only expressed, or are overexpressed, in tumor cells compared with non‐tumor tissue, thereby reducing the side effects of chemotherapy . For example, the epidermal growth factor receptor (EGFR) is overexpressed or abnormally expressed in many solid tumors (e.g., non‐small cell lung cancer, prostate cancer, breast cancer and melanoma) . Song et al .…”

“…62 For example, the epidermal growth factor receptor (EGFR) is overexpressed or abnormally expressed in many solid tumors (e.g., non-small cell lung cancer, prostate cancer, breast cancer and melanoma). [63][64][65][66][67] Song et al designed GE11-modified liposomes that can combine specifically and effectively with non-small cell lung cancer cells overexpressing EGFR. 68 The A375 human melanoma cells express large amounts of integrin avb3; therefore, targeting this molecule could increase the intake of nanomedicines.…”