Histone deacetylase inhibitor induced modulation of anti-estrogen therapy.
Histone deacetylase (HDAC) inhibitors are a novel class of anti-tumor agents with a potential role in the treatment of breast cancer. In ER-positive cells, treatment with selective and non-selective HDAC inhibitors has been associated with a transcriptional down-regulation (and possibly protein modification via the HSP90 chaperone function) of ER and its response genes. In ER-negative cell lines, HDAC inhibitors have been shown to re-establish ER expression. In addition, HDAC inhibitors have been reported to modulate the progesterone receptor. Despite the opposing effects in ER-positive and ER-negative breast cancer cells, the addition of an HDAC inhibitor potentiated and restored the efficacy of anti-estrogen therapy in preclinical models. This has led to the initiation of several clinical trials combining HDAC inhibitors with anti-estrogen therapy. In this review, we will summarize the relationship between estrogen signaling and HDACs, examine how HDAC inhibitors impact this relationship and synergize with anti-estrogens to inhibit tumor growth, and discuss the clinical possibilities and potential of this new approach.
Thomas
Scott
S
Division of Hematology and Oncology, University of California, San Francisco San Francisco, CA 94143, United States.
Munster
Pamela N
PN
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D004357:Drug Synergism; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D056572:Histone Deacetylase Inhibitors; D011960:Receptors, Estrogen; D006655:Histone Deacetylases