title: The potential role of PD0332991 (Palbociclib) in the treatment of multiple myeloma.
abstract: BACKGROUND
  Multiple myeloma (MM) remains an incurable malignancy indicating a need for continued investigation of novel therapies. Recent studies have highlighted the role of cyclin-dependent kinases (CDK) in the pathogenesis of MM. PD0332991 (Palbociclib) is an orally bioavailable, highly selective inhibitor of the CDK4/6-cyclin complex and downstream retinoblastoma protein (Rb) activation pathway that induces cell cycle arrest in the G1 phase.
  
  
  METHODS
  In this review, the authors summarize the role of the CDK4/6 signaling pathway in MM. They also summarize the development of PD0332991 as a specific inhibitor of CDK4/6, and the reported preclinical and clinical data supporting the potential role of PD0332991 in MM.
  
  
  CONCLUSIONS
  While PD0332991 is essentially cytostatic, inducing prolonged G1 arrest, it enhances the cytotoxic effect of other agents effective in MM, including bortezomib and lenalidomide, as confirmed in early phase clinical trials. However, with a plethora of other drugs of different classes being tested in MM, further development of PD0332991 will depend on defining the most efficacious combination with least toxicity. An unexplored opportunity remains the potential protective effect of PD0332991 against lytic bone lesions of MM. The next few years are likely to better define the place of PD0332991 in the treatment of MM.
authors.affiliation: Indiana University School of Medicine, Department of Microbiology and Immunology , Indianapolis, IN , USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Altenburg
authors.forename: Sherif S
authors.initials: SS
authors.lastname: Farag
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D018844:Cyclin-Dependent Kinases; C500026:palbociclib
keywords: CDK4/6; cell cycle; multiple myeloma