In vivo visualization of fluorescence reflecting CDK4 activity in a breast cancer mouse model. Issue 3 (10th June 2022)

• Record Type: Journal Article
• Authors: Gao, Yi‐Yang; Yang, Rui‐Qin; Lou, Kang‐Liang; Dang, Yong‐Ying; Dong, Yuan‐Yuan; He, Yue‐Yang; Huang, Wen‐He; Chen, Min; Zhang, Guo‐Jun
• Is Part Of: MedComm. Volume 3:Issue 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-10
• Subjects: breast cancer -- CDK4 inhibitors -- fluorescence imaging -- kinase activity -- therapeutic evaluation; 610
• DOI: 10.1002/mco2.136
• Languages: English
• ISSNs: 2688-2663

Abstract

Abstract: The CDK4/6‐Rb axis is a crucial target of cancer therapy and several selective inhibitors of it have been approved for clinical application. However, current therapeutic efficacy evaluation mostly relies on anatomical imaging, which cannot directly reflect changes in drug targets, leading to a delay in the selection of optimal treatment. In this study, we constructed a novel fluorescent probe, CPP30‐Lipo/CDKACT4, for real‐time monitoring of CDK4 activity and the therapeutic efficacy of its inhibitor in HR + /HER2 – breast cancer. CPP30‐Lipo/CDKACT4 exhibited good optical stability and targetability. The signal of the probe in living cells decreased after CDK4 knockdown or palbociclib treatment. Moreover, the fluorescence intensity of the tumors after 7 days of palbociclib treatment was significantly lower than that before treatment, while no significant change in tumor diameter was observed under magnetic resonance imaging. Overall, we developed an innovative fluorescent probe that can monitor CDK4 activity and the early therapeutic response to CDK4 inhibitors in living cells and in vivo . It may provide a new strategy for evaluating antitumor therapeutic efficacy in a clinical context and for drug development. Abstract : In this study, we utilized a unique targeting delivery strategy that encapsulated the peptide biosensor CDKACT4 into CPP30‐modified DOPE cationic liposomes to obtain a novel and stable fluorescent probe, CPP30‐Lipo/CDKACT4. It realized the visualization of CDK4 activity in living cells and in vivo, and initially assessed the therapeutic efficacy of CDK4 inhibitors in the treatment of HR + /HER2 ‐ breast cancer in pre‐clinical experiments. This study provides a novel thought for the assessment of clinical drug therapeutic efficacy and accurate guidance of individualized antitumor therapy, as well as offering a new tool for the development of antitumor drugs.