Gianni L, Lladó A, Bianchi G et al.
Istituto Nazionale Tumori, Milan, Italy.
J Clin Oncol 2010;28:1131–7.
[2] Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy.
Baselga J, Gelmon KA, Verma S et al.
Vall d’Hebron University Hospital, Barcelona, Spain.
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[3] Whither HER2-related therapeutics?
De P, Leyland-Jones B.
Emory University, Atlanta, GA, USA.
J Clin Oncol 2010;28:1091–6.
Editor’s note: There has been a great deal of interest in the development of HER2-directed therapies following the adoption of agents such as trastuzumab in the treatment of both metastatic and early stage breast cancer. However, some patients are primarily resistant to trastuzumab and many develop resistance following exposure to treatment. While considerable advances have been made in HER2-directed therapy, exploitation of other members of the EGFR family has been less successful. The two Phase II trials [1,2] and associated editorial [3] reviewed here address the use of another antibody to HER2. This antibody, pertuzumab, is directed against a different epitope of the extracellular domain of HER2 to trastuzumab. Its principal mode of action seems to be to inhibit dimerization of HER2 with other monomers of the EGFR family. Since HER2 dimerizes preferentially with HER3 (which has known ligands but no active tyrosine kinase domain) and also with HER1, it was originally suggested that such inhibitors of heterodimerization might have activity in tumors that express HER2 at “normal” levels by preventing signal transduction mediators through HER3 and HER1.