| First Author | Sherr CJ | Year | 2016 |
| Journal | Cancer Discov | Volume | 6 |
| Issue | 4 | Pages | 353-67 |
| PubMed ID | 26658964 | Mgi Jnum | J:236841 |
| Mgi Id | MGI:5807341 | Doi | 10.1158/2159-8290.CD-15-0894 |
| Citation | Sherr CJ, et al. (2016) Targeting CDK4 and CDK6: From Discovery to Therapy. Cancer Discov 6(4):353-67 |
| abstractText | Biochemical and genetic characterization of D-type cyclins, their cyclin D-dependent kinases (CDK4 and CDK6), and the polypeptide CDK4/6 inhibitor p16(INK4)over two decades ago revealed how mammalian cells regulate entry into the DNA synthetic (S) phase of the cell-division cycle in a retinoblastoma protein-dependent manner. These investigations provided proof-of-principle that CDK4/6 inhibitors, particularly when combined with coinhibition of allied mitogen-dependent signal transduction pathways, might prove valuable in cancer therapy. FDA approval of the CDK4/6 inhibitor palbociclib used with the aromatase inhibitor letrozole for breast cancer treatment highlights long-sought success. The newest findings herald clinical trials targeting other cancers. SIGNIFICANCE: Rapidly emerging data with selective inhibitors of CDK4/6 have validated these cell-cycle kinases as anticancer drug targets, corroborating longstanding preclinical predictions. This review addresses the discovery of these CDKs and their regulators, as well as translation of CDK4/6 biology to positive clinical outcomes and development of rational combinatorial therapies. |
