CDK4 and cancer: While alterations leading to increased D-type cyclin levels have been suggested as potential biomarkers for sensitivity to CDK4/6 inhibitors in cancer cell lines [36], this was not observed for primary breast cancer [69], and data suggest that high levels of cyclin D might also desensitize cells to CDK4/6 blockade by formation of cyclin D-CDK2 complexes which are expected to be insensitive to CDK4/6 inhibitors [40].