Mechanisms of tamoxifen resistance.
The anti-oestrogen tamoxifen is the most commonly used treatment for patients with oestrogen-receptor (ER)-positive breast cancer. Although many patients benefit from tamoxifen in the adjuvant and metastatic settings, resistance is an important clinical problem. The target of tamoxifen in vivo is the ER. Over the last decade many advances have been made in our understanding of the biology of the ER which may help to explain how resistance to tamoxifen develops. Such mechanisms may include changes in the expression of ERalpha or ERbeta, alterations in co-regulatory proteins, and the influences of cellular kinase signal transduction pathways. The experimental and clinical evidence supporting these mechanisms of tamoxifen resistance are discussed in this review.
Ring
Alistair
A
Academic Department of Biochemistry, Royal Marsden Hospital, Fulham Rd, London. SW3 6JJ, UK.
Dowsett
Mitch
M
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D013629:Tamoxifen / Q000627:therapeutic use*; D014158:Transcription, Genetic
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen