Possible mechanisms in the emergence of tamoxifen-resistant breast cancer.
Tamoxifen (TAM), a non-steroidal antiestrogen, is the endocrine treatment of choice for all stages of breast cancer. However, despite a favorable initial response to therapy, most tumors will eventually exhibit TAM resistance resulting in disease recurrence. Several mechanisms of TAM resistance have been proposed, yet a single distinct mechanism has not been identified. We will systematically consider the following steps of the estrogen receptor (ER)-mediated signal transduction pathway to identify possible sites of alteration leading to tamoxifen-resistance: (1) ligand metabolism and availability, (2) loss or mutation of the ER, (3) defects in ER post-translational modification, and (4) alteration of the estrogen response element (ERE). In particular, the ERE will be discussed as a position in the signal transduction pathway with considerable potential, if altered, to confer TAM resistance.
Tonetti
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DA
Robert H Lurie Cancer Center, Northwestern University Medical School, Chicago, IL 60611, USA.
Jordan
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VC
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D004351:Drug Resistance; D006801:Humans; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen