CDK4, CDK6/cyclin-D1 Complex Inhibition and Radiotherapy for Cancer Control: A Role for Autophagy

Abstract

The expanding clinical application of CDK4- and CDK6-inhibiting drugs in the managements of breast cancer has raised a great interest in testing these drugs in other neoplasms. The potential of combining these drugs with other therapeutic approaches seems to be an interesting work-ground to explore. Even though a potential integration of CDK4 and CDK6 inhibitors with radiotherapy (RT) has been hypothesized, this kind of approach has not been sufficiently pursued, neither in preclinical nor in clinical studies. Similarly, the most recent discoveries focusing on autophagy, as a possible target pathway able to enhance the antitumor efficacy of CDK4 and CDK6 inhibitors is promising but needs more investigations. The aim of this review is to discuss the recent literature on the field in order to infer a rational combination strategy including cyclin-D1/CDK4-CDK6 inhibitors, RT, and/or other anticancer agents targeting G1-S phase cell cycle transition.

PIMREG is a prognostic biomarker involved in immune microenvironment of clear cell renal cell carcinoma and associated with the transition from G1 phase to S phase

“…The activities of cyclin dependent kinases 4 and 6 (CDK4 and CDK6) are also essential to the cell cycle. They form a complex with cyclin D1 to jointly regulate tumor proliferation, and this complex is becoming a new target for tumor therapy ( 23 , 24 ). Previous studies have reported that the knockdown of PIMREG can inhibit the proliferation of prostate cancer, glioma and breast cancer cells by prolonging G1 cell phase ( 9 , 13 , 14 ).…”

Studies on Chemical Composition of Pueraria lobata and Its Anti-Tumor Mechanism

“…CDK, cyclin-dependent protein kinase, is a group of serine/threonine protein kinases [ 33 ]. CDK drives the cell cycle through chemotaxis on serine/threonine proteins and acts synergistically with cyclin, an important factor in cell cycle regulation, and CDK4 is an important isoform in the family [ 34 ]. A large number of studies have found that drugs can inhibit the growth of tumor cells by suppressing the expression of cyclins such as CCND1 and CDK4.…”

Identification of Enhancer RNA CDK6-AS1 as a Potential Novel Prognostic Biomarker in Gastric Cancer

“…CDK6 (cyclin-dependent kinases 6), could form complexes D-type cyclins (D1, D2 and D3) and progress cells to early G1 phase (22). CDK4/6-cyclin D complexes is regulated by Cip/Kip proteins which had impacted on nuclear translocation of complexes (23,24). Some researches had reported that overexpression of CDK6 could affect on lymphoma, leukemia and other malignancies.…”