title: De novo resistance biomarkers to anti-HER2 therapies in HER2-positive breast cancer.
abstract: Therapies targeting HER2 receptor, overexpressed in 20% breast cancer (BC), improved prognosis, however ~62% patients experiment progression during the first year. Molecular mechanisms proposed to be responsible for this de novo resistance include HER2 modifications, defects in the antibody dependent cellular cytotoxicity or in cell arrest and apoptosis or alterations in HER2 signaling components. This article will review the influence of genetic markers investigated to date as cause of de novo resistance to HER2-targeted drugs in HER2-positive BC patients. Biomarkers like p95HER2, CCND1 and CDC25A have demonstrated clinical relevance and prognostic value in HER2-positive BC patients. However, the prognostic value of most biomarkers investigated to date, such as PIK3CA or AKT1, cannot be fully established yet.
authors.affiliation: Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain.|Department of Biochemistry & Molecular Biology II, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, s/n, 18071 Granada, Spain.
authors.forename: Adela
authors.initials: A
authors.lastname: Madrid-Paredes
authors.affiliation: Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain.
authors.forename: Marisa
authors.initials: M
authors.lastname: Cañadas-Garre
authors.affiliation: Department of Biochemistry & Molecular Biology II, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, s/n, 18071 Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sánchez-Pozo
authors.affiliation: Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain.|Department of Pharmacology, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, s/n; 18071 Granada, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Calleja-Hernández
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: HER2-targeted therapies; breast cancer; lapatinib; pharmacogenetics; resistance; trastuzumab