title: Advances in mechanisms of resistance to aromatase inhibitors.
abstract: Clinically, there are two distinct types of aromatase inhibitor (AI) resistance, namely acquired and innate resistance. Because the underlying mechanisms of these two types of resistance may not be mutually exclusive, strategies to tackle these resistances may not be effective when used interchangeably. Activation of growth factor receptor pathways is the hallmark of acquired AI resistance. These pathways can be targeted either at the cell surface receptor level or their downstream signaling cascades. Currently, everolimus in combination with exemestane represents a new standard of care for patients progressing on non-steroidal AIs. HDAC inhibitors have also shown promising results For innate resistance, the combination of fulvestrant and AI in the front line setting represents a new treatment option, particularly for patients who present with de novo metastatic disease. A Phase III trial is currently ongoing to evaluate the benefit of CDK 4/6 inhibitor, palbociclib, in the first line setting in combination with AI.
authors.affiliation: Department of Medicine, University of Maryland, School of Medicine and the Greenebaum Cancer Center, Baltimore, MD, USA.
authors.forename: Saranya
authors.initials: S
authors.lastname: Chumsri
authors.forename: Amanda
authors.initials: A
authors.lastname: Schech
authors.forename: Chakkapong
authors.initials: C
authors.lastname: Chakkabat
authors.forename: Gauri
authors.initials: G
authors.lastname: Sabnis
authors.forename: Angela
authors.initials: A
authors.lastname: Brodie
mesh_terms: D000818:Animals; D047072:Aromatase Inhibitors / Q000145:classification / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D044127:Epigenesis, Genetic; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D047072:Aromatase Inhibitors; D006655:Histone Deacetylases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011960:Receptors, Estrogen; D017978:Receptors, Growth Factor; D058570:TOR Serine-Threonine Kinases; D019061:src-Family Kinases; C546842:MTOR protein, human