title: Dinaciclib for the treatment of breast cancer.
abstract: BACKGROUND
  Cyclin-dependent kinases (CDK) represent attractive targets in oncology due to their key role in controlling gene transcription and cell cycle progression. Dinaciclib (MK-7965, formerly SCH727965) is a relatively novel CDK 1/2/5/9 inhibitor that has shown promising results in preclinical studies and an acceptable safety profile in Phase I clinical trials. It is currently under clinical evaluation for the treatment of hematological and solid malignancies, including breast cancer.
  
  
  METHODS
  This review summarizes the current understanding of CDK's role in physiology and cancer, and the therapeutic value of blocking their pathways in breast cancer. Particularly, the article reviews the preclinical and clinical data for dinaciclib in its use for the treatment of breast cancer.
  
  
  CONCLUSIONS
  A better understanding of the molecular mechanisms underlying cell cycle dysregulation in cancer is needed in order to develop novel CDK inhibitors. Additionally, further efforts are needed to identify potential biomarkers of dinaciclib efficacy, which could allow a better selection of patients enrolled in clinical trials. Moreover, combination therapies with dinaciclib or other CDK and chemotherapy, endocrine therapy or targeted therapies might be further evaluated in breast cancer patients.
authors.affiliation: Istituto Europeo di Oncologia, Division of Early Drug Development for Innovative Therapies , Via Ripamonti 435, 20133 Milano , Italy +39 02 57489439 ; +39 02 94379224 ; giuseppe.curigliano@ieo.it.
authors.forename: Carmen
authors.initials: C
authors.lastname: Criscitiello
authors.forename: Giulia
authors.initials: G
authors.lastname: Viale
authors.forename: Angela
authors.initials: A
authors.lastname: Esposito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D003497:Cyclic N-Oxides; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D005260:Female; D006801:Humans; D007212:Indolizines; D018579:Patient Selection; D011726:Pyridinium Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003497:Cyclic N-Oxides; D007212:Indolizines; D011726:Pyridinium Compounds; C553669:dinaciclib; D018844:Cyclin-Dependent Kinases
keywords: breast cancer; cyclin-dependent kinases; cyclin-dependent kinases inhibitors; dinaciclib