ERK1/2 inhibition increases antiestrogen treatment efficacy by interfering with hypoxia-induced downregulation of ERalpha: a combination therapy potentially targeting hypoxic and dormant tumor cells.
Tumor hypoxia is associated with cancer invasiveness, metastasis and treatment failure. Recent data suggest that the major target for endocrine treatment in breast cancer, ER alpha, is downregulated during hypoxia, but the mechanism behind this remains unknown. MAPK signaling as well as ER alpha regulation has earlier been independently linked to hypoxia and we now demonstrate HIF-1 alpha and ERK1