title: Cell cycle control as a promising target in melanoma.
abstract: OBJECTIVE
  This review highlights recent clinical developments in the therapeutic targeting of cell cycle control in melanoma with cyclin-dependent kinase inhibitors, checkpoint kinases, MDM2, MDM4 and p53 inhibitors.
  
  
  RESULTS
  The high prevalence of activating genetic aberrations along the p16 INK4A:cyclinD-CDK4/6:RB pathway in melanoma and increasing evidence that alterations in this pathway are linked to melanomagenesis, make targeting the p16 INK4A:cyclinD-CDK4/6:RB pathway in melanoma logical and highly attractive. The presence of elevated CDK4 activity appears to correlate with greater CDK4/6 inhibitor therapeutic activity, whereas the loss of RB1 has been linked to CDK inhibitor resistance. Other novel compounds targeting cell cycle control via reactivating wild-type p53 and checkpoint kinases are also currently under investigation in melanoma.
  
  
  CONCLUSIONS
  Cell cycle control is a promising target in the management of melanoma with early data reporting therapeutic benefit with cyclin-dependent kinase inhibitors, MDM2, and p53 reactivation compounds. Many of these drugs have entered phase I and II clinical trial development. Preliminary data from these studies are discussed in this review along with future treatment strategies for maximizing treatment outcomes in advanced melanoma.
  http://links.lww.com/COON/A12.
authors.affiliation: aDepartment of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne bDepartment of Pathology, University of Melbourne, Parkville cDepartment of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy dMolecular Oncology Laboratory, Oncogenic Signalling and Growth Control Program eTranslational Research Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Lee
authors.forename: Shahneen
authors.initials: S
authors.lastname: Sandhu
authors.forename: Grant
authors.initials: G
authors.lastname: McArthur
mesh_terms: D002352:Carrier Proteins; D002453:Cell Cycle / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000037:antagonists & inhibitors*; D018450:Disease Progression; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051358:Cyclin-Dependent Kinase 4