title: Reactivation of p53 as therapeutic intervention for malignant melanoma.
abstract: OBJECTIVE
  Targeted therapy of malignant melanoma recently experienced remarkable advances with gene mutation-based therapies with signaling pathway inhibitors (kinase inhibitors). The treatments prolong patients' survival, but in general resistance is acquired and progression of disease occurs. Therefore, additional therapeutic targets are desperately needed.
  
  
  RESULTS
  The p53 tumor suppressor gene is rarely mutated in melanoma, but its functional attenuation is needed for tumor development. Recently, it was found that the essential p53 inhibitor Mdmx is very frequently overexpressed in melanoma. Mdmx displays both p53-dependent and p53-independent oncogenic effects needed for melanoma growth
  
  
  CONCLUSIONS
  Current melanoma therapy based upon kinase inhibitors shows robust initial clinical effect, but the duration of effect is limited. Inactivation of Mdmx in melanoma inhibits tumor growth also of kinase-inhibitor-resistant tumors. An observed synergistic effect of kinase-inhibition and Mdmx targeting can lead to better and more durable treatment of melanoma patients.
authors.affiliation: Department of Molecular Cell Biology, Leiden, The Netherlands.
authors.forename: Aart G
authors.initials: AG
authors.lastname: Jochemsen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D047428:Protein Kinase Inhibitors; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2