Signal integration: a framework for understanding the efficacy of therapeutics targeting the human EGFR family.
The human EGFR (HER) family is essential for communication between many epithelial cancer cell types and the tumor microenvironment. Therapeutics targeting the HER family have demonstrated clinical success in the treatment of diverse epithelial cancers. Here we propose that the success of HER family-targeted monoclonal antibodies in cancer results from their ability to interfere with HER family consolidation of signals initiated by a multitude of other receptor systems. Ligand/receptor systems that initiate these signals include cytokine receptors, chemokine receptors, TLRs, GPCRs, and integrins. We further extrapolate that improvements in cancer therapeutics targeting the HER family are likely to incorporate mechanisms that block or reverse stromal support of malignant progression by isolating the HER family from autocrine and stromal influences.
Shepard
H Michael
HM
Receptor BioLogix, Inc., Palo Alto, California 94303, USA. hms@rblx.com
Brdlik
Cathleen M
CM
Schreiber
Hans
H
D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors