title: Combined cancer therapy: strategies to overcome acquired aromatase inhibitor resistance.
abstract: Aromatase inhibitors (AIs) have become one of the mainstays of treatment of postmenopausal women with hormone receptorpositive breast cancer. However, acquired resistance to treatment continues to be a significant clinical challenge. There is increasing evidence from preclinical studies that activation of growth factor signaling pathways, as well as cross-talk between these pathways and estrogen receptor-alpha signaling pathways are important mechanisms that contribute to AI resistance. These preclinical studies have been the foundation for multiple randomized clinical trials that have evaluated combination targeted therapy in patients with advanced breast cancer. While the clinical benefit observed in these trials has been variable, the preclinical studies were successful in predicting clinical outcomes. This review focuses on mechanisms of acquired AI resistance and describes preclinical studies that have evaluated combination targeted therapy to overcome AI resistance, as well as clinical trials that have translated this information to the clinical setting.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Kesmodel
authors.forename: Gauri J
authors.initials: GJ
authors.lastname: Sabnis
authors.forename: Saranya
authors.initials: S
authors.lastname: Chumsri
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Health Science Facility-I, Room 580G, 685 W. Baltimore St., Baltimore, MD 21201. abrodie@umaryland.edu.
authors.forename: Angela M H
authors.initials: AM
authors.lastname: Brodie
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors