Annals of Oncology Advance Access originally published online on January 17, 2007
Annals of Oncology 2007 18(6):977-984; doi:10.1093/annonc/mdl475
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2007 European Society for Medical Oncology
reviews |
Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer
University Division of Medical Oncology and Haematology, Institute for Cancer Research and Treatment, Strada Provinciale 142, 10060 Candiolo, Torino, Italy
* Correspondence to: Dr G. Valabrega, University Division of Medical Oncology and Haematology, Institute for Cancer Research and Treatment (IRCC). Tel: +39-119933253; Fax: +39-0119933299; E-mail: giorgio.valabrega{at}ircc.it
Trastuzumab is a humanized mAb directed against the extracellular domain of the tyrosine kinase receptor HER2. Trastuzumab has shown clinical activity in HER2-overexpressing breast cancers and, at present, is currently approved for patients whose tumours have this abnormality, in both the metastatic and the adjuvant setting. Several issues about its optimal use, however, are still unresolved. One of the reasons for these uncertainties lies in the absence of conclusive data about its mechanism of action and possible primary or acquired resistance mechanisms. Therefore, clinical questions such as how to optimize patient selection, how to prevent resistance to trastuzumab, or what is the optimal management of those patients whose tumours progress during treatment still await convincing answers. This review summarises the current knowledge on the preclinical and clinical evidence about the mechanism of action of trastuzumab and on the mechanisms underlying the development of resistance and also briefly discusses their possible clinical implications.
Key words: breast neoplasms, HER2, mechanism of action, resistance, trastuzumab
Received for publication May 25, 2006. Revision received September 11, 2006. Accepted for publication November 30, 2006.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  U. McDermott and J. Settleman Personalized Cancer Therapy With Selective Kinase Inhibitors: An Emerging Paradigm in Medical Oncology J. Clin. Oncol., November 20, 2009; 27(33): 5650 - 5659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Valabrega, M. Aglietta, and F. Montemurro Trastuzumab Beyond Disease Progression: Case Closed? J. Clin. Oncol., September 20, 2009; 27(27): e121 - e122. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nagumo, D. Faratian, P. Mullen, D. J. Harrison, M. Hasmann, and S. P. Langdon Modulation of HER3 Is a Marker of Dynamic Cell Signaling in Ovarian Cancer: Implications for Pertuzumab Sensitivity Mol. Cancer Res., September 1, 2009; 7(9): 1563 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. McLarty, B. Cornelissen, Z. Cai, D. A. Scollard, D. L. Costantini, S. J. Done, and R. M. Reilly Micro-SPECT/CT with 111In-DTPA-Pertuzumab Sensitively Detects Trastuzumab-Mediated HER2 Downregulation and Tumor Response in Athymic Mice Bearing MDA-MB-361 Human Breast Cancer Xenografts J. Nucl. Med., August 1, 2009; 50(8): 1340 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Shah, T. W. Miller, S. K. Wyatt, E. T. McKinley, M. G. Olivares, V. Sanchez, D. D. Nolting, J. R. Buck, P. Zhao, M. S. Ansari, et al. Imaging Biomarkers Predict Response to Anti-HER2 (ErbB2) Therapy in Preclinical Models of Breast Cancer Clin. Cancer Res., July 15, 2009; 15(14): 4712 - 4721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Schoeberl, E. A. Pace, J. B. Fitzgerald, B. D. Harms, L. Xu, L. Nie, B. Linggi, A. Kalra, V. Paragas, R. Bukhalid, et al. Therapeutically Targeting ErbB3: A Key Node in Ligand-Induced Activation of the ErbB Receptor-PI3K Axis Sci. Signal., June 30, 2009; 2(77): ra31 - ra31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gori, A. Sidoni, M. Colozza, I. Ferri, M. G. Mameli, D. Fenocchio, L. Stocchi, J. Foglietta, V. Ludovini, E. Minenza, et al. EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry: correlation with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab Ann. Onc., April 1, 2009; 20(4): 648 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Sabnis, A. Schayowitz, O. Goloubeva, L. Macedo, and A. Brodie Trastuzumab Reverses Letrozole Resistance and Amplifies the Sensitivity of Breast Cancer Cells to Estrogen Cancer Res., February 15, 2009; 69(4): 1416 - 1428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. King, J. Waxman, and H. Stauss Advances in tumour immunotherapy QJM, September 1, 2008; 101(9): 675 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Costantini, K. Bateman, K. McLarty, K. A. Vallis, and R. M. Reilly Trastuzumab-Resistant Breast Cancer Cells Remain Sensitive to the Auger Electron-Emitting Radiotherapeutic Agent 111In-NLS-Trastuzumab and Are Radiosensitized by Methotrexate J. Nucl. Med., September 1, 2008; 49(9): 1498 - 1505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Najy, K. C. Day, and M. L. Day The Ectodomain Shedding of E-cadherin by ADAM15 Supports ErbB Receptor Activation J. Biol. Chem., June 27, 2008; 283(26): 18393 - 18401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. J. Dahabreh, H. Linardou, F. Siannis, G. Fountzilas, and S. Murray Trastuzumab in the Adjuvant Treatment of Early-Stage Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Oncologist, June 1, 2008; 13(6): 620 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Shattuck, J. K. Miller, K. L. Carraway III, and C. Sweeney Met Receptor Contributes to Trastuzumab Resistance of Her2-Overexpressing Breast Cancer Cells Cancer Res., March 1, 2008; 68(5): 1471 - 1477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Varchetta, N. Gibelli, B. Oliviero, E. Nardini, R. Gennari, G. Gatti, L. S. Silva, L. Villani, E. Tagliabue, S. Menard, et al. Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients Under Trastuzumab Therapy for Primary Operable Breast Cancer Overexpressing Her2 Cancer Res., December 15, 2007; 67(24): 11991 - 11999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Liu, T. Deng, R. S. Lehal, J. Kim, and E. Zacksenhaus Identification of Tumorsphere- and Tumor-Initiating Cells in HER2/Neu-Induced Mammary Tumors Cancer Res., September 15, 2007; 67(18): 8671 - 8681. [Abstract] [Full Text] [PDF]
|
|