Trastuzumab decreases the number of circulating and disseminated tumor cells despite trastuzumab resistance of the primary tumor.
We have recently shown that despite of the fact that the ErbB2-positive JIMT-1 human breast cancer cells intrinsically resistant to trastuzumab in vitro, trastuzumab inhibited the outgrowth of early phase JIMT-1 xenografts in SCID mice via antibody-dependent cellular cytotoxicity (ADCC). Here we show that trastuzumab significantly reduces the number of circulating and disseminated tumor cells (CTCs and DTCs) in this xenograft model system at a time when the primary tumor is already unresponsive to trastuzumab. This observation suggests that ErbB2 positive CTCs and DTCs might be sensitive to trastuzumab-mediated ADCC even if when the primary tumor is already non-responsive. Thus, trastuzumab treatment might also be beneficial in the case of patients with breast cancer that is already trastuzumab resistant.
Barok
Márk
M
Department of Biophysics and Cell Biology, University of Debrecen, 4012 Debrecen, Egyetem ter 1., Hungary. barokm@dote.hu
Balázs
Margit
M
Nagy
Péter
P
Rákosy
Zsuzsa
Z
Treszl
Andrea
A
Tóth
Eniko
E
Juhász
István
I
Park
John W
JW
Isola
Jorma
J
Vereb
György
G
Szöllosi
János
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000069283:Rituximab; D013997:Time Factors; D000068878:Trastuzumab; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D000069283:Rituximab; C512478:EGFR protein, human; D066246:ErbB Receptors; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D000068878:Trastuzumab