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CDK4, CDK6/cyclin-D1 Complex Inhibition and Radiotherapy for Cancer Control: A Role for Autophagy
Authors:Valerio Nardone  Marcella Barbarino  Antonio Angrisani  Pierpaolo Correale  Pierpaolo Pastina  Salvatore Cappabianca  Alfonso Reginelli  Luciano Mutti  Clelia Miracco  Rocco Giannicola  Antonio Giordano  Luigi Pirtoli
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.
Keywords:cyclin inhibitors   radiotherapy   autophagy
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