Cdk 4/6 inhibitors revolutionized breast cancer therapy

Abstract

The cyclin-CDK inhibitors of the Cip/Kip family p21Cip1, p27Kip1, and p57Kip2 have emerged as multifaceted proteins with functions beyond cell cycle regulation. They are used to treat cancers by preventing over proliferation of cancer cells. In metazoans, two CKI gene families have been defined based on their evolutionary origins, structure, and CDK specificities. A vast body of literature has described the importance of p21, p27, and p57 in restraining proliferation during development, differentiation, and response to cellular stresses, although each has specific biological functions that distinguish it from the other family members. Thus, different anti-proliferative signals tend to cause elevated expression of only a subset of the Cip/Kip proteins. Following a recent and detailed review on the subject. We concentrate our attention on an updated list of compounds under clinical evaluation (phase I/II/III) and discuss their mode of action as ATP-competitive inhibitors Also, tentative progress for forthcoming potential ATP non-competitive inhibitors and allosteric inhibitors will be discussed.