title: Investigational ErbB-2 tyrosine kinase inhibitors for the treatment of breast cancer.
abstract: BACKGROUND
  ErbB2 overexpression and/or gene amplification is present in 20% of all breast cancers and characterizes an aggressive form of this disease. Despite the availability of several active drugs that have yielded substantial survival improvements, most patients with ErbB2-positive metastatic disease will develop tumor progression, either because of primary or acquired resistance. Therefore, research has focused on drugs that can more efficiently interfere with ErbB2 and with other members of the epidermal growth factor receptor family.
  
  
  METHODS
  This review focuses on those investigational drugs that inhibit ErbB2 tyrosine kinase activity (TKIs) for treating breast cancer.
  
  
  CONCLUSIONS
  ErbB-targeting TKIs show encouraging activity in patients with ErbB-positive tumors that are resistant to conventional ErbB-therapies (mostly trastuzumab), confirming pre-clinical observations. Efficient interference with the ErbB-network signaling implies also a potential use in ErbB2-normal tumors, where the phenotype is sustained by ErbB-aberrant signaling. Finally, early data suggests that ErbB-targeting TKIs could be active in treating patients with activating ErbB2 mutations. Ongoing and future research efforts should elucidate what is, according to the peculiarities of these compounds, their positioning in the treatment of women with breast cancer.
authors: a Department of Investigative Clinical Oncology (INCO) , Fondazione del Piemonte per l'Oncologia (FPO) - Candiolo Cancer Institute (IRCCs) , Candiolo , Italy.|b University of Turin Medical School, Department of Medical Oncology at Fondazione del Piemonte per l'Oncologia (FPO) - Candiolo Cancer Institue (IRCCs) , Candiolo , Italy.
authors: Rossella
authors: R
authors: Martinello
authors: a Department of Investigative Clinical Oncology (INCO) , Fondazione del Piemonte per l'Oncologia (FPO) - Candiolo Cancer Institute (IRCCs) , Candiolo , Italy.
authors: Andrea
authors: A
authors: Milani
authors: a Department of Investigative Clinical Oncology (INCO) , Fondazione del Piemonte per l'Oncologia (FPO) - Candiolo Cancer Institute (IRCCs) , Candiolo , Italy.
authors: Elena
authors: E
authors: Geuna
authors: a Department of Investigative Clinical Oncology (INCO) , Fondazione del Piemonte per l'Oncologia (FPO) - Candiolo Cancer Institute (IRCCs) , Candiolo , Italy.
authors: Giorgia
authors: G
authors: Zucchini
authors: a Department of Investigative Clinical Oncology (INCO) , Fondazione del Piemonte per l'Oncologia (FPO) - Candiolo Cancer Institute (IRCCs) , Candiolo , Italy.|b University of Turin Medical School, Department of Medical Oncology at Fondazione del Piemonte per l'Oncologia (FPO) - Candiolo Cancer Institue (IRCCs) , Candiolo , Italy.
authors: Caterina
authors: C
authors: Aversa
authors: a Department of Investigative Clinical Oncology (INCO) , Fondazione del Piemonte per l'Oncologia (FPO) - Candiolo Cancer Institute (IRCCs) , Candiolo , Italy.
authors: Annamaria
authors: A
authors: Nuzzo
authors: a Department of Investigative Clinical Oncology (INCO) , Fondazione del Piemonte per l'Oncologia (FPO) - Candiolo Cancer Institute (IRCCs) , Candiolo , Italy.
authors: Filippo
authors: F
authors: Montemurro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D015507:Drugs, Investigational / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D053634:TYK2 Kinase / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D047428:Protein Kinase Inhibitors; D053634:TYK2 Kinase
keywords: Breast cancer; ErbB1; ErbB2; ErbB3; ErbB4; tyrosine-kinase inhibitors