Understanding the mechanisms of trastuzumab efficacy and resistance is a step toward optimizing treatment outcome in HER2-positive breast carcinoma patients. Preclinical studies have indicated different trastuzumab antitumor mechanisms, that is, cytostatic inhibition of tumor proliferation, antibody-dependent cell cytotoxicity, and inhibition of HER2-mediated DNA repair. Clinical studies point to the clinical setting dependence of these mechanisms, with antibody-dependent cell cytotoxicity predominating when trastuzumab is used as monotherapy in neoadjuvant and metastatic settings, whereas inhibition of DNA repair predominates in neoadjuvant and adjuvant settings involving concomitant trastuzumab and chemotherapy; in sequential protocols, the antibody appears to act primarily through cytostatic activity by inhibiting HER2-mediated cell proliferation. Because the mechanisms of resistance to trastuzumab likely depend directly on those of its antitumor activity, resistance mechanisms must also be considered with respect to the different clinical settings. Moreover, the response to this reagent should be assessed according to its ability to induce tumor cytotoxic or cytostatic activity.
|Titolo:||The HER2 World: better treatment selection for better outcome|
BALSARI, ANDREA (Penultimo)
|Parole Chiave:||Molecular Targeted Therapy ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; Cell Proliferation ; Clinical Trials as Topic ; DNA Repair ; Disease Progression ; Drug Synergism ; Female ; Humans ; Neoadjuvant Therapy ; Patient Selection ; Receptor, erbB-2 ; Tumor Markers, Biological|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2011|
|Digital Object Identifier (DOI):||10.1093/jncimonographs/lgr041|
|Appare nelle tipologie:||01 - Articolo su periodico|