title: Targeted therapy in brain metastasis.
abstract: OBJECTIVE
  To review the state of the art and new developments in the field of targeted agents for brain metastases.
  
  
  RESULTS
  The huge amount of information on new molecular compounds and the advances in understanding the molecular pathways that mediate brain colonization have led to an increase of interest in preclinical and clinical investigations in the field of brain metastases. Targeted therapies can be employed either on established brain metastases or in a prevention setting. Targeting angiogenesis is an attractive approach. Up to date, large clinical trial datasets have shown that antiangiogenic agents do not increase the risk of bleeding into the brain. Bevacizumab (an anti-VEGF agent) is undergoing investigation in clinical trials on brain metastases from non-small cell lung cancer (NSCLC), breast cancer and melanoma. Sunitinib, a multitarget small molecule tyrosine kinase inhibitor (TKI), is a promising agent in brain metastases from renal cell cancer. The EGFR inhibitors gefitinib and erlotinib have a definite activity in brain metastases from NSCLC with activating EGFR mutations. Regarding HER2-positive breast cancer patients with established brain metastases, lapatinib (small molecule TKI) seems particularly active in association with capecitabine. Lapatinib alone is attractive in the prevention setting. Brain metastases from melanoma with BRAF V600E mutations respond to a specific inhibitor, such as vemurafenib. The immunomodulator ipilimumab is also active on brain metastases from melanoma.
  
  
  CONCLUSIONS
  The use of targeted agents in brain metastases from solid tumors is promising. The setting of prevention will be probably expanded in the next years. Well designed clinical trials with proper endpoints are needed.
authors: Division of Neuro-oncology, Department of Neuroscience, University and San Giovanni Battista Hospital, Torino, Italy. riccardo.soffietti@unito.it
authors: Riccardo
authors: R
authors: Soffietti
authors: Elisa
authors: E
authors: Trevisan
authors: Roberta
authors: R
authors: Rudà
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000556:secondary*; D002986:Clinical Trials as Topic; D006801:Humans; D000074324:Ipilimumab; D000077341:Lapatinib; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D000077341:Lapatinib; D011799:Quinazolines; C500926:cediranib; D007211:Indoles