Steroid receptors and immunophilin relationships in hormone-dependent cancers - Use of long-circulation anti-steroid hormone and/or immunosuppressantcarriers as a promising therapeutic approach

Steroid hormones like oestrogens, progestins and androgens act as key induc ers and modulators of cell proliferation, differentiation and reproduction. They bind specifically to receptors which are tissue specific transcriptio n factors, In human hormone dependent-breast and prostate cancers, antihorm ones are used clinically to compete for the biological activity of the natu ral hormone. Orally administered, these drugs ale of poor biological availa bility and can also induce severe sine effects. In breast cancer, the antio estrogen tamoxifen is used as first-line hormonotherapy, but resistance and increased risk of uterus cancers have been reported. Unliganded steroid re ceptors associate to immunophilins which binds the immunosuppressive drugs cyclosporin A or FK506 or rapamycin. These drugs, as well as antihormones i nduce the silencing of genes involved in cell proliferation control; their combined use in hormone-dependent cancer could constitute a promising appro ach for developing new therapy. To that purpose, they can be incorporated i n "long-circulating" (with high vascular remanence) carriers which can be r endered "active" by coupling to recognition ligands. Such a new way of anti -cancer drug delivery for hormone-dependent cancers would decrease the amou nt of active principles, and increase their efficacy due to targeting of th e nanocapsules to the tumoural site(s).