[Genetic testing for effective Herceptin therapy].
Herceptin has provided the first proof that tyrosine kinase modulation, through monoclonal antibodies can translate into improved clinical outcomes in cancer therapy. The development of Herceptin was encouraged by the biologic significance of HER2 overexpression. Although the number of patients affected by the targeted molecular abnormality(30% of breast cancer patients) is small and the response rate observed in patients after treated with single agent Herceptin is rather low, the ability to document overexpression of the target in breast biopsies, and a growing interest in biologic therapy facilitated the rapid accrual of patients to clinical trials. The challenges of applying research techniques of molecular biology to routine clinical testing have been demonstrated by the experiences with the HER2/neu oncogene. Immunohistochemistry and fluorescence in situ hybridization yielded discrepant results regarding the frequency and degree of HER2 alterations even within the same sample. In order to make the complexity of interpretation of the discrepancy simple, it is wise to build an algorithm to help clinicians follow the ideal sequence of laboratory testings. The experience gained in the testing of Herceptin has provided important lessons for the future testing of molecularly targeted compounds.
Watanabe
Toru
T
Department of Medical Oncology, National Cancer Center Hospital.
Katsumata
Noriyuki
N
Ando
Masashi
M
Mukai
Hirofumi
H
Shimizu
Chikako
C
Kitagawa
Ryo
R
Saijo
Nagahiro George
NG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D021141:Nucleic Acid Amplification Techniques; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab