TY - JOUR
T1 - HER3, serious partner in crime Therapeutic approaches and potential biomarkers for effect of HER3-targeting
AU - Kol, Arjan
AU - Terwisscha Van Scheltinga, Anton
AU - Timmer-Bosscha, Hetty
AU - Lamberts, Laetitia E.
AU - Bensch, Frederike
AU - de Vries, Elisabeth
AU - Schroder, Carolina P.
PY - 2014/7
Y1 - 2014/7
N2 - The human epidermal growth factor receptor (HER) family members are targeted by a growing numbers of small molecules and monoclonal antibodies. Resistance against the epidermal growth factor receptor (EGFR) and HER2-targeting agents is a clinically relevant problem forcing research on optimizing targeting of the HER family. In view of its overexpression in tumors, and compensatory role in HER signaling, HER3 has gained much interest as a potential additional target within the HER family. It is the only member of the HER family lacking intrinsic tyrosine kinase activity and therefore its role in cancer has long been underestimated. Drugs that block HER3 or interfere with HER3 dimer signaling, including fully human anti-HER3 antibodies, bispecific antibodies and tyrosine kinase inhibitors (TKIs), are currently becoming available. Several compounds have already entered clinical trial. In the meantime potential biomarkers are tested such as tumor analysis of HER3 expression, functional assays for downstream effector molecules and molecular imaging techniques. This review describes the biology and relevance of HER3 in cancer, agents targeting HER3 and potential biomarkers for effect of HER3-targeting. (C) 2014 Elsevier Inc. All rights reserved.
AB - The human epidermal growth factor receptor (HER) family members are targeted by a growing numbers of small molecules and monoclonal antibodies. Resistance against the epidermal growth factor receptor (EGFR) and HER2-targeting agents is a clinically relevant problem forcing research on optimizing targeting of the HER family. In view of its overexpression in tumors, and compensatory role in HER signaling, HER3 has gained much interest as a potential additional target within the HER family. It is the only member of the HER family lacking intrinsic tyrosine kinase activity and therefore its role in cancer has long been underestimated. Drugs that block HER3 or interfere with HER3 dimer signaling, including fully human anti-HER3 antibodies, bispecific antibodies and tyrosine kinase inhibitors (TKIs), are currently becoming available. Several compounds have already entered clinical trial. In the meantime potential biomarkers are tested such as tumor analysis of HER3 expression, functional assays for downstream effector molecules and molecular imaging techniques. This review describes the biology and relevance of HER3 in cancer, agents targeting HER3 and potential biomarkers for effect of HER3-targeting. (C) 2014 Elsevier Inc. All rights reserved.
KW - HER3
KW - Molecular imaging
KW - Biomarkers
KW - Monoclonal antibodies
KW - Tyrosine kinase inhibitors
KW - Resistance
KW - EPIDERMAL-GROWTH-FACTOR
KW - METASTATIC BREAST-CANCER
KW - C-ERBB-3 PROTEIN EXPRESSION
KW - RESISTANT OVARIAN-CANCER
KW - FACTOR RECEPTOR FAMILY
KW - AFATINIB BIBW 2992
KW - TYROSINE KINASE
KW - EGF RECEPTOR
KW - CELL-PROLIFERATION
KW - ANTITUMOR-ACTIVITY
U2 - 10.1016/j.pharmthera.2014.01.005
DO - 10.1016/j.pharmthera.2014.01.005
M3 - Review article
SN - 0163-7258
VL - 143
SP - 1
EP - 11
JO - Pharmacology & Therapeutics
JF - Pharmacology & Therapeutics
IS - 1
ER -