Recent Progress in CDK4/6 Inhibitors and PROTACs

Abstract

Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based on their structural characteristics and origins. Furthermore, it explores proteolysis targeting chimers (PROTACs) targeting CDK4/6. We hope that this review could be of benefit for further research on CDK4/6 inhibitors and PROTACs.

Advances in Nanodynamic Therapy for Cancer Treatment

“…In addition, Wang et al introduced a novel carrier-free NP that amalgamates CDK4/6 PROTAC with Ce6-mediated PDT, achieving the self-assembly of both compounds (Figure 3). This combination, with CDK4/6 PROTAC acting as a G1-S phase checkpoint inhibitor [69], reinforces mitochondria-dependent PDT and its anti-tumor immune consequences, leading to increased apoptosis and immunogenic cell death [33]. This study offers a pioneering approach by combining PDT with immune checkpoint inhibition, revealing a potent anti-tumor methodology through meticulous drug delivery and targeting of mitochondrial functions.…”

KRAS G12C inhibitor combination therapies: current evidence and challenge

“…CDK4/6 is regulated by D-type cyclins and CDK inhibitor p16. CDK4/6 inhibitors are effective as a treatment for breast cancer ( 64 ). The activation of CDK4/6 plays a role in KRAS G12C inhibitor resistance through co-alteration of CDKN2A and increased activation from collateral pathways such as the PI3K–AKT–mTOR pathway ( 24 , 61 ).…”

Synthesis and Preclinical Evaluation of Novel 68Ga-DOTA-RBB as Potential PET Radiotracer for Imaging CDK4/6 in Tumors

“…CDK4/6 inhibitors play a crucial role in blocking the activation of CDK4/6 by interfering with the growth and proliferation of cancer cells . To the best of our knowledge, this is the first research report utilizing 68 Ga-labeled ribociclib analogues for CDK4/6 imaging.…”