In this study, we used computational methods and The Cancer Genome Atlas dataset analysis to identify novel miRNAs that target CDK4/6 and exhibit potential for therapeutic development in colorectal cancer.
On real cancer data, pathTiMEx recapitulates previous knowledge on tumorigenesis, such as the temporal order among pathways which include APC, KRAS, and TP53 in colorectal cancer, while also proposing new biological hypotheses, such as the existence of a single early causal event consisting of the amplification of CDK4 and the deletion of CDKN2A in glioblastoma. pathTiMEx is available as an R package.
Autophagy induction by CDK4 inhibitor was observed in BT474, MDA-MB435S, SKBr3 (derived from breast cancer), A431 (derived from epidermoid cancer), and SW480 (derived from colorectal cancer) cell lines.
Combined inhibition of both MEK and CDK4/6 is effective in preclinical models of KRAS mutant CRC and justifies a planned phase II clinical trial in patients with refractory KRAS-mutant CRC.Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models.
We suggest that CDK4, together with JNK, alters tumor-suppressive TGF-beta signaling to malignant characteristics in later stages of human colorectal cancer.
These results support the experimental evidence that interaction of expression of p16 and CDK4 may play an important role in the Rb/p16 pathway, and the expression patterns of CDK4 and p16 may be imperative in the development of colorectal carcinoma, thus becoming a new prognostic marker in colorectal cancer.