TARGETING CDK4 AND CDK6: FROM DISCOVERY TO THERAPY

By C. Sherr, D. Beach, G. Shapiro. Cancer Discovery, 2015

796 citations recorded by the source corpus.

Biochemical and genetic characterization of D-type cyclins, their cyclin D-dependent kinases (CDK4 and CDK6), and the polypeptide CDK4/6 inhibitor p16INK4 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 (RB)-dependent manner. These investigations provided proof-of-principle that CDK4/6 inhibitors, particularly when combined with co-inhibition 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.

Subfields: Oncology, Pathology and Forensic Medicine, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/4355484f403ede6a4409dbe3d440573cfc34c4b8

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Citations in the corpus

• Cyclin D1, Cancer Progression and Opportunities in Cancer Treatment (2016, background): “Besides breast cancers, these inhibitors are undergoing extensive investigations in various clinical trials; the activities and efforts to evaluate CDK4/CDK6 inhibitors in a variety of indications have recently been reviewed in depth [1].”
• Mechanisms and functions of cellular senescence. (2018, neutral): “Conversely, drugs that induce senescence (such as palbociclib and other CDK4/6 inhibitors) have shown significant benefits as anticancer agents (125).”