title: Tamoxifen Resistance: Emerging Molecular Targets.
abstract: 17β-Estradiol (E2) plays a pivotal role in the development and progression of breast cancer. As a result, blockade of the E2 signal through either tamoxifen (TAM) or aromatase inhibitors is an important therapeutic strategy to treat or prevent estrogen receptor (ER) positive breast cancer. However, resistance to TAM is the major obstacle in endocrine therapy. This resistance occurs either de novo or is acquired after an initial beneficial response. The underlying mechanisms for TAM resistance are probably multifactorial and remain largely unknown. Considering that breast cancer is a very heterogeneous disease and patients respond differently to treatment, the molecular analysis of TAM's biological activity could provide the necessary framework to understand the complex effects of this drug in target cells. Moreover, this could explain, at least in part, the development of resistance and indicate an optimal therapeutic option. This review highlights the implications of TAM in breast cancer as well as the role of receptors/signal pathways recently suggested to be involved in the development of TAM resistance. G protein-coupled estrogen receptor, Androgen Receptor and Hedgehog signaling pathways are emerging as novel therapeutic targets and prognostic indicators for breast cancer, based on their ability to mediate estrogenic signaling in ERα-positive or -negative breast cancer.
authors.affiliation: Department of Medical Sciences, University of Turin, Turin 10126, Italy. srondonl@unito.it.
authors.forename: Milena
authors.initials: M
authors.lastname: Rondón-Lagos
authors.affiliation: Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 11001000, Colombia. victoria.villegas@urosario.edu.co.|Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogotá 11001000, Colombia. victoria.villegas@urosario.edu.co.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Villegas
authors.affiliation: Department of Medical Sciences, University of Turin, Turin 10126, Italy. nrangel@unito.it.|Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 11001000, Colombia. nrangel@unito.it.|Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogotá 11001000, Colombia. nrangel@unito.it.
authors.forename: Nelson
authors.initials: N
authors.lastname: Rangel
authors.affiliation: Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 11001000, Colombia. magda.sanchez@urosario.edu.com.
authors.forename: Magda Carolina
authors.initials: MC
authors.lastname: Sánchez
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge 14183, Sweden. peter.zaphiropoulos@ki.se.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Zaphiropoulos
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D013629:Tamoxifen
keywords: G protein-coupled estrogen receptor (GPER); Hedgehog (HH) signaling pathway; androgen receptor (AR); breast cancer; endocrine resistance; estrogen receptors (ERs); tamoxifen