Epigenetic regulation in estrogen receptor positive breast cancer--role in treatment response.
Recent advances in breast cancer treatment have allowed increasing numbers of patients with estrogen receptor (ER) positive (+) breast cancer to receive various forms of endocrine therapy. Unfortunately, de novo and acquired resistance to endocrine therapy remains a major challenge in the clinic. A number of possible mechanisms for drug resistance have been described, which include activation of growth factor receptor pathways, overexpression of ER coactivators, and metabolic resistance due to polymorphisms in metabolizing enzymes. While many of these changes are caused by genetic alterations, there is also increasing evidence to implicate epigenetic gene regulatory mechanisms in the development of endocrine resistance. Since epigenetic modifications are easier to reverse than genetic mutations, they are appealing therapeutic targets, and thus future improvements in medical care for breast cancer patients will depend upon a better understanding of the roles epigenetic modifications play in endocrine resistance. In this review we will focus on recent advances made in the understanding of epigenetic gene regulation in estrogen response and endocrine resistance in breast cancer. We will also summarize current clinical-translational advances in epigenetic therapy, and discuss potential future clinical use of epigenetic changes as therapeutic targets, especially with respect to endocrine treatment.
Pathiraja
Thushangi N
TN
Translational Biology and Molecular Medicine Graduate Program, Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Stearns
Vered
V
Oesterreich
Steffi
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D056572:Histone Deacetylase Inhibitors; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone