title: Synergy of molecular targeted approaches and immunotherapy in melanoma: preclinical basis and clinical perspectives.
abstract: BACKGROUND
  Targeted therapy and immunotherapies are the novel pharmacologic treatment strategies for metastatic melanoma. BRAF and MEK inhibitors effectively block the hyperactivation of the MAPK pathway in BRAF mutant melanomas and also have several other effects on melanoma cells and on the immune response. The aim of this work is to discuss the rationale, evidence and perspectives of approaches combining target and immunotherapy against melanoma.
  
  
  METHODS
  We first review the effects of BRAF and MEK inhibitors on melanoma cells and on the different components of the immune system. Afterwards, we summarize the results of the preclinical and clinical studies that have combined targeted therapy and immunotherapy for the treatment of melanoma.
  
  
  CONCLUSIONS
  Clinical applications of immunotherapy strategies have recently changed the therapeutic mainstay for metastatic melanoma. Biologic and initial preclinical data support their integration with innovative molecular targeted therapies, opening enormous perspectives for researchers in the effort of finding a definitive cure. Main open challenges are the definition of reliable research models, assessment of effective schedules, safety issues and designing of personalized approaches.
authors.affiliation: a 1 University of Turin, Department of Medical Sciences, Section of Dermatology , Via Cherasco 23, Torino, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Sanlorenzo
authors.affiliation: b 2 University of California San Francisco, Mt. Zion Cancer Research Center , 2340 Sutter Street N461, San Francisco, CA, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Vujic
authors.affiliation: b 2 University of California San Francisco, Mt. Zion Cancer Research Center , 2340 Sutter Street N461, San Francisco, CA, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Moy
authors.affiliation: a 1 University of Turin, Department of Medical Sciences, Section of Dermatology , Via Cherasco 23, Torino, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Quaglino
authors.affiliation: a 1 University of Turin, Department of Medical Sciences, Section of Dermatology , Via Cherasco 23, Torino, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Fierro
authors.affiliation: c 3 Candiolo Cancer Institute FPO- IRCCS, Division and Laboratory of Medical Oncology , Candiolo, Torino, Italy.
authors.forename: Loretta
authors.initials: L
authors.lastname: Gammaitoni
authors.affiliation: c 3 Candiolo Cancer Institute FPO- IRCCS, Division and Laboratory of Medical Oncology , Candiolo, Torino, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carnevale-Schianca
authors.affiliation: d 4 University of Torino, Department of Oncology , Torino, Italy +390119933503 ; +390119933522 ; dario.sangiolo@ircc.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
authors.affiliation: b 2 University of California San Francisco, Mt. Zion Cancer Research Center , 2340 Sutter Street N461, San Francisco, CA, USA.|c 3 Candiolo Cancer Institute FPO- IRCCS, Division and Laboratory of Medical Oncology , Candiolo, Torino, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Sangiolo
mesh_terms: D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007167:Immunotherapy; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases
keywords: BRAF inhibitors; immunotherapy; melanoma; targeted therapy