title: A recombinant decoy comprising EGFR and ErbB-4 inhibits tumor growth and metastasis.
abstract: Epidermal growth factor (EGF)-like growth factors control tumor progression as well as evasion from the toxic effects of chemotherapy. Accordingly, antibodies targeting the cognate receptors, such as EGFR/ErbB-1 and the co-receptor HER2/ErbB-2, are widely used to treat cancer patients, but agents that target the EGF-like growth factors are not available. To circumvent the existence of 11 distinct ErbB ligands, we constructed a soluble fusion protein (hereinafter: TRAP-Fc) comprising truncated extracellular domains of EGFR/ErbB-1 and ErbB-4. The recombinant TRAP-Fc retained high-affinity ligand binding to EGF-like growth factors and partially inhibited growth of a variety of cultured tumor cells. Consistently, TRAP-Fc displayed an inhibitory effect in xenograft models of human cancer, as well as synergy with chemotherapy. Additionally, TRAP-Fc inhibited invasive growth of mammary tumor cells and reduced their metastatic seeding in the lungs of animals. Taken together, the activities displayed by TRAP-Fc reinforce critical roles of EGF-like growth factors in tumor progression, and they warrant further tests of TRAP-Fc in preclinical models.
authors: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors: M
authors: M
authors: Lindzen
authors: S
authors: S
authors: Carvalho
authors: A
authors: A
authors: Starr
authors: N
authors: N
authors: Ben-Chetrit
authors: C-R
authors: CR
authors: Pradeep
authors: W J
authors: WJ
authors: Köstler
authors: A
authors: A
authors: Rabinkov
authors: S
authors: S
authors: Lavi
authors: S S
authors: SS
authors: Bacus
authors: Y
authors: Y
authors: Yarden
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000737:chemistry*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D066247:Receptor, ErbB-4; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; D011993:Recombinant Fusion Proteins; C587689:ERBB4 protein, human; C587690:Erbb4 protein, mouse