The selective estrogen enzyme modulator (SEEM) in breast cancer.
Human breast cancer tissue contains all the enzymes (estrone sulfatase, 17beta-hydroxysteroid dehydrogenase, aromatase) involved in the last steps of estradiol biosynthesis. This tissue also contains sulfotransferase for the formation of the biologically inactive estrogen sulfates. In the last years, it was demonstrated that various progestins (promegestone, nomegestrol acetate, medrogestone), as well as tibolone and its metabolites are potent inhibitors of sulfatase and 17beta-hydroxysteroid dehydrogenase activities. It was also shown that medrogestone, nomegestrol acetate, promegestone or tibolone can stimulate the sulfotransferase activity for the local production of estrogen sulfates. All these data, in addition to numerous agents, which can block the aromatase action, lead to the new concept of selective estrogen enzyme modulators (SEEM), which can largely apply to breast cancer tissue. The exploration of various progestins and other active agents in trials with breast cancer patients, showing an inhibitory effect on sulfatase and 17beta-hydroxysteroid dehydrogenase, or a stimulatory effect on sulfotransferase, will provide a new possibility in the treatment of this disease.
Chetrite
G S
GS
Hormones and Cancer Research Unit, 26 Blvd Brune, 75014, Paris, France.
Pasqualini
J R
JR
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D001141:Aromatase / Q000187:drug effects* / Q000378:metabolism; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D006801:Humans; D011374:Progesterone / Q000037:antagonists & inhibitors; D013429:Sulfatases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D020847:Estrogen Receptor Modulators; D011374:Progesterone; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; D013429:Sulfatases; C020121:estrone sulfatase