Pertuzumab protects the achilles' heel of trastuzumab--emtansine.
Trastuzumab emtansine (T-DM1) represents a significant advancement in the treatment of HER2(+) breast cancers. Its clinical efficacy however will be limited by the development of therapeutic resistance. In this report, the HER3 ligand neuregulin is shown to mediate T-DM1 resistance, which was overcome by administration of pertuzumab, a steric inhibitor of HER2 dimerization.
Authors' Affiliation: Department of Medicine, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.
William R
WR
Gwin
Neil L
NL
Spector
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D020880:Neuregulins / Q000037:antagonists & inhibitors*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D020880:Neuregulins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C485206:pertuzumab