[Hormone resistance and its modulation in breast cancer].
Acquired hormone resistance is a reversible adaptative change of hormone-sensitive breast tumors promoting survival by changes in the balance and communication between estrogen receptor and growth factor signaling. The mechanisms of hormone resistance induced by various hormone therapies are different, however, their common feature is the dominance of growth factor signaling with the consequences of enhanced proliferation and decreased apoptosis. In case of tamoxifen or selective estrogen receptor modulator resistance, the agents' enhanced agonistic activity occurs. The increased expression of certain estrogen receptor coactivators may play an important role. The essential of hormone resistance after estrogen deprivation is estrogen hypersensitivity, which is a consequence of the enhanced activity of the membrane-associated estrogen receptor and its influence on the growth factor signaling. The integration of cell surface growth factor receptor or growth factor signal transduction blocking agents like tyrosine kinase, MAPK, mTOR, PI3K or farnesyl transferase inhibitors into hormone therapies may prevent or treat hormone resistance. The other possibility is to use the hormone therapies sequentially. A new promising agent is the pure antiestrogen fulvestrant which targets the estrogen receptor located in both the membrane or the nucleus. Also, estrogen therapy may revert hormone resistance. The use of predictive markers may promote treatment choice and indicate application of targeted therapies.
Kahán
Zsuzsanna
Z
Szegedi Tudományegyetem, Szent-Györgyi Albert Orvos- és Gyógyszerésztudományi Centrum, Altalános Orvostudományi Kar, Onkoterápiás Klinika, Szeged.
Thurzó
László
L
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D020239:Receptor Cross-Talk / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use
D006133:Growth Substances; D007155:Immunologic Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen