Bevacizumab treatment nullifies Bax up-regulation induced by epirubicin and docetaxel chemotherapy in human breast cancer.
Chemotherapeutics utilized in breast cancer, including taxane drugs such as docetaxel, exert their function through a variety of mechanisms; one of these is the induction of apoptotic genes (1) like those of the Bcl-2 family (2). We found through mining published data from the Phase II PROMIX trial (3) that treatment with epirubicin and docetaxel chemotherapy resulted in the induction of the Bcl-2 family gene Bax (4) which functions in the execution of cell death. However, following addition of bevacizumab to the treatment regimen, Bax expression returned to levels even lower than at baseline. This was not the case in glioblastoma patients treated with bevacizumab, demonstrating tissue-specific function of bevacizumab in human cancer (5). Thus, in patients with breast cancer, bevacizumab antagonizes activation of cell death gene expression induced by epirubicin and docetaxel chemotherapy, demonstrating an undesirable effect of a therapeutic utilized for the treatment of cancer - a disease, a major feature of which is the acquired ability to evade death signaling (6).