The effect of trastuzumab/docatexel combination on breast cancer angiogenesis: dichotomus effect predictable by the HIFI alpha/VEGF pre-treatment status?

摘要: In this study we describe and discuss the dichotomous effects of docetaxel trastuzumab (Herceptin)/docetaxel therapy on angiogenic molecular profile in two patients with her-2 + chemo-resistant recurrent breast carcinoma. first case, an intensification angiogenesis occurred following therapy, accompanied by impressive increase cancer cell proliferation index. This tumor did not express HIF1 alpha shared a HIF-independent VEGF overexpression, which remained unaffected therapy. An intensified formation thymidine phosphorylase (TP)-rich stroma, presumably response to docetaxel, shows TP-dependent response. second patient, were down-regulated post-treatment biopsies was sharp reduction vascular density rate. both cases, c-erbB-2 expression abrogated Herceptin. Taking into account that Herceptin down-regulates through synthesis, clinical provides evidence anti-angiogenic effect from Herceptin/Docetaxel is expected only tumors alpha-dependent overexpression. contrast, alpha-independent activity cannot be Docetaxel mediated up-regulation TP tumoral stroma may, contrary, result intersification rapid relapse. Such should importance since Herceptin/Docetaxel-based regimens are currently evaluated for adjuvant patients. Studying Herceptin-induced phenotypic changes could lead identification specific profiles bring about diverging responses. Adjustment chemotherapy regimen accordingly would prove importance.