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Despite extensive diagnostic and therapeutic efforts, breast cancer remains the second leading cause of female cancer mortality in affluent countries. Because receptor tyrosine kinases of the Epidermal Growth Factor Receptor [EGFR, also ErbB] family are potent gatekeepers of cell fate decisions, their aberrations rank among the most frequent oncogenic insults in breast cancers. Although monoclonal...
Her-2-positive breast cancers are associated with higher recurrence rates and increased mortality. Trastuzumab, a humanised monoclonal antibody targeting the extracellular domain of Her-2, is an important part of palliative first-line therapy. Combination therapy with taxanes improved response rates, progression-free as well as overall survival. Based on those results, different groups initiated...
The amplification and expression of ERBB2 have been linked with prognosis and response to therapy with the anti-HER-2-humanised monoclonal antibody, trastuzumab, in patients with advanced metastatic breast cancer. However, one of the major clinical problems encountered with trastuzumab treatment is that metastatic breast cancer patients, who initially responded to trastuzumab, showed disease progression...
Trastuzumab is the first antibody that has shown clinical activity in patients with HER-2-positive breast cancer. The mechanism of action is not fully understood; however, antibody-derived cellular cytotoxicity (ADCC) is considered to explain important peculiarities of its clinical activity such as treatment beyond progression. Based on early pre-clinical data, trastuzumab was used beyond progression...
Pertuzumab is a recombinant humanised monoclonal antibody targeting the extracellular domain of human epidermal growth factor receptor 2 (HER-2) to block HER-2 dimerisation with other HER family members. Preclinical pertuzumab data showed activity in a number of solid tumour types, and synergistic or additive activity was also observed when pertuzumab was combined with chemotherapy or with other targeted...
Growth factor receptors of the ErbB family play key roles in transmitting mitogenic and anti-apoptotic signals in epithelial cells. Aberrant activation of these pathways by a variety of mechanisms, including receptor over-expression due to gene amplification and activating mutations in receptors or downstream signal transducers, contributes to tumourigenesis, invasion and tumour angiogenesis. Consequently,...
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