Emerging strategies for ErbB ligand-based targeted therapy for cancer.
ErbB receptors are crucial for development and evolution and have been intensely pursued as targets for cancer therapeutics. Inhibiting the signaling activity of individual receptors in this family has advanced human cancer treatment. However, actual curative effects of the existing anti-ErbB therapeutics are still insufficient. A large percentage of patients who are initially responsive to ErbB receptor-targeted therapies later become resistant. Mechanisms responsible for tumor resistance to ErbB-targeted agents are as follows: many epidermal growth factor receptor (EGFR)- and HER2-targeted therapies cannot inhibit signaling through the ErbB receptor heterodimer, and anti-EGFR agents can suppress extracellular signal-related kinase (ERK) signal proliferation but not protein kinase B/Akt survival signals. ErbB ligand-based targeted therapy against HB-EGF or amphiregulin may overcome such obstacles. Here we discuss the efficacy of CRM197, a specific inhibitor of HB-EGF, and its possible clinical adaptation in combination with conventional chemotherapeutic agents in cancer therapy.
Tsujioka
Hiroshi
H
Department of Obstetrics and Gynecology, Fukuoka University Faculty of Medicine Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. tsujioka@fukuoka-u.ac.jp
Yotsumoto
Fusanori
F
Shirota
Kyoko
K
Horiuchi
Shinji
S
Yoshizato
Toshiyuki
T
Kuroki
Masahide
M
Miyamoto
Shingo
S
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects*
D000970:Antineoplastic Agents; D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases