CDK inhibitors as potential breast cancer therapeutics: new evidence for enhanced efficacy in ER+ disease

Loss of cell cycle control is a hallmark of cancer, and aberrations in the cyclin-CDK-RB (cyclin-dependent kinase-retinoblastoma protein) pathway are common in breast cancer. Consequently, inhibition of this pathway is an attractive therapeutic strategy, but results from clinical trials of CDK inhibitors in breast cancer have been disappointing. A recent study now shows that in cell culture a selective CDK4/6 inhibitor is preferentially effective in estrogen receptor-positive (ER(+)) disease and apparently acts synergistically with tamoxifen or trastuzumab. These exciting new preclinical data set the scene for a more targeted approach to further clinical evaluation wherein this class of drugs is targeted to subgroups of ER(+) patients, including those with resistance to endocrine therapy, alone or in combination with current standard therapies.