title: Targeted therapy with kinase inhibitors in aggressive endocrine tumors.
abstract: BACKGROUND
  Kinase inhibitors (KIs) are a class of anticancer drugs that inhibit activity of the enzymes protein kinases, which regulate crucial cellular processes and have a demonstrated role in human oncogenesis. Treatment of advanced forms of endocrine cancer which are not responsive to cytotoxic chemotherapies is challenging and use of KIs is gaining a growing role in this field.
  
  
  METHODS
  The authors summarize the main genetic alterations known to be linked to endocrine tumors, indicating the rationale for utilizing KIs. Furthermore, they present an updated analysis of clinical trials available on PubMed Central, which were pertinent to the activities of KIs in aggressive endocrine cancer. The authors also discuss the adverse effects of KIs and summarize likely involved underlying mechanisms.
  
  
  CONCLUSIONS
  KIs are effective in obtaining a radiological disease control and an improvement of progression-free survival in several forms of endocrine cancer but will never deliver a knockout blow of the disease, due to mechanisms of adaptation to circumvent the specific molecular blockade. The new frontier of KIs treatment is to identify agents that could synergize activity of KIs. The true goal will be to perform an overall genotyping of each tumor, thus predicting the impact of combined targeted therapies in the context of a particular constellation of mutant genes.
authors.affiliation: Federico II University, Department of Clinical Medicine and Surgery, Italy. vinc.endo@libero.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Marotta
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Franzese
authors.forename: Michela
authors.initials: M
authors.lastname: Del Prete
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Chiofalo
authors.forename: Valeria
authors.initials: V
authors.lastname: Ramundo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Esposito
authors.forename: Francesca
authors.initials: F
authors.lastname: Marciello
authors.forename: Luciano
authors.initials: L
authors.lastname: Pezzullo
authors.forename: Annachiara
authors.initials: A
authors.lastname: Carratù
authors.forename: Mario
authors.initials: M
authors.lastname: Vitale
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Antongiulio
authors.initials: A
authors.lastname: Faggiano
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors