A pan-HER approach for cancer therapy: background, current status and future development.
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.


CONCLUSIONS
RB200, a bispecific (EGFR/HER3) ligand binding trap, has been developed to address the need for a pan-HER therapy in human cancer.
Huang
Zhongdong
Z
Receptor BioLogix, Inc., Palo Alto, CA 94303, USA.
Brdlik
Cathleen
C
Jin
Pei
P
Shepard
H Michael
HM
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C485206:pertuzumab