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Abstract
Background: The human EGF receptor (EGFR or HER) family and its cognate ligands contribute significantly to the aggressiveness of many human malignancies, and are therefore therapeutic targets with great clinical potential. Objective: Currently approved single-targeted agents, like mAbs, (e.g., trastuzumab, cetuximab, or pertuzumab) or small-molecule tyrosine kinase inhibitors (TKIs, e.g., gefinitib and erlotinib), are limited by their exquisite specificity (mAbs) or lack thereof (TKIs). Therefore, therapeutics are needed that target multiple HER family members and HER ligands to circumvent these limitations. Methods: We summarize therapeutic mechanisms of action, analyze tumor resistance to current anti-HER therapies, and introduce a novel pan-HER ligand sequestering agent for cancer treatment. Conclusion: RB200, a bispecific (EGFR/HER3) ligand binding trap, has been developed to address the need for a pan-HER therapy in human cancer.
Acknowledgements
The authors wish to thank Scott Patton for illustrations, editing and preparation of this manuscript.