The Potential of panHER Inhibition in Cancer

Purpose: Hyper-activation of the HER (erbB) family receptors, HER 1-4, leads to up-regulation of the three vital signaling pathways: mitogen activated protein kinase, phosphoinositide 3-kinase/AKT, and Janus kinase/signal transducer and activator of transcription pathways. Blocking HER1/EGFR has a limited anticancer effect due to either secondary mutation e.g., T790M or by-pass signaling of other HER members. The emergence of an anti-panHER approach to blockade of these pathways as a cancer treatment may provide a solution to this resistance. This review aimed to provide an overview of the HER signaling pathways and their involvement in tumor progression and examine the current progress in panHER inhibition. Methods: Recent literature associated with HER signaling pathways and panHER inhibition was reviewed through PubMed and Medline database, followed by critical comparison and analysis. Results: Pre-clinical studies and clinical trials of panHER inhibitors show promising results, and the potential to improve patient outcomes in solid cancers. Conclusion: The use of panHER inhibitors in cancers with HER-family hyper-activation, such as other epithelial cancers and sarcoma, is a new direction to research and has potential in clinical cancer therapy in the future.