title: Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?
abstract: In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc.) significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.
authors.affiliation: Department of Oncology and Hematology, University Hospital of Modena and Reggio Emilia, via del Pozzo 71, 41121 Modena, Italy. angela.toss@unimore.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Toss
authors.affiliation: Department of Oncology and Hematology, University Hospital of Modena and Reggio Emilia, via del Pozzo 71, 41121 Modena, Italy. martaventurelli@msn.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Venturelli
authors.affiliation: Department of Oncology and Hematology, University Hospital of Modena and Reggio Emilia, via del Pozzo 71, 41121 Modena, Italy. chiara.peterle@gmail.com.
authors.forename: Chiara
authors.initials: C
authors.lastname: Peterle
authors.affiliation: Department of Oncology and Hematology, University Hospital of Modena and Reggio Emilia, via del Pozzo 71, 41121 Modena, Italy. federico.piacentini@unimore.it.
authors.forename: Federico
authors.initials: F
authors.lastname: Piacentini
authors.affiliation: Department of Oncology and Hematology, University Hospital of Modena and Reggio Emilia, via del Pozzo 71, 41121 Modena, Italy. stefano.cascinu@unimore.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Department of Oncology and Hematology, University Hospital of Modena and Reggio Emilia, via del Pozzo 71, 41121 Modena, Italy. hbc@unimore.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Cortesi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: breast cancer; molecular biomarker; targeted therapy; treatment resistance