Tamoxifen non-estrogen receptor mediated molecular targets

Abstract

Recent experimental studies revealing new biological effects of tamoxifen on tumor cells both expressing and not expressing different types of estrogen receptors (ERα and ERβ) show new aspects of a seemingly well known agent. This review describes tamoxifen targets, the blocking of which leads to inhibition of tumor cell growth and angiogenesis, stimulation of programmed cell death (apoptosis, autophagia and necrosis), inhibition of multidrug resistance, invasion and metastasis. Since outcomes of tamoxifen action on cells are prognostically good from the point of view of both tumor growth/metastasis inhibition and tumor response to drug therapy, the authors believe this is an extremely important addition to tamoxifen antiestrogenic effect. Arguments are provided to consider the strategy of long-term tamoxifen treatment proposed by Professor Craig V. Jordan in the 1970s that is also applicable to the treatment of other tumors. This is, first of all, the fact that expression of estrogen receptor-beta that can also be targeted by tamoxifen therapy in solid tumors of practically all known sites and histologies. The authors believe that molecular biological screening of patients with respect to expression of tamoxifen cellular targets other than ERα and ERβ is needed to use to the full all tamoxifen biological activities other than modulation of estrogen receptors during long-term adjuvant therapy for cancers of various sites.