Unveiling novel therapeutic avenues: Targeting the cyclin D/CDK4 axis for enhanced cancer treatment

The deregulation of the cyclin D/CDK complex is a prevalent feature in various cancer types, including colorectal cancer, breast cancer, and melanoma, leading to uncontrolled cell cycle progression and tumor growth. Targeting the cyclin D/CDK complex has emerged as a promising therapeutic strategy for cancer treatment. CDK4 inhibitors, such as ribociclib, palbociclib, and abemaciclib, have demonstrated clinical efficacy by disrupting the interaction between cyclin D and CDK4, essential for Retinoblastoma protein (pRb) phosphorylation and cell cycle progression. However, developing resistance to CDK4 inhibitors underscores the need for more potent alternatives. This hypothesizes that targeting the cyclin D/CDK axis can unveil novel therapeutic options surpassing the limitations of current cancer treatments. Conventional approaches like chemotherapy, radiation therapy, and CDK inhibitors exhibit efficacy but often have adverse side effects. By focusing on the cyclin D/CDK axis, this hypothesis aims to identify innovative strategies that offer greater selectivity, potency, and reduced side effects. Understanding the molecular mechanisms underlying cyclin D/CDK dysregulation in cancer is pivotal in advancing oncology therapeutics. The solution involves structural mining, molecular dynamics (MD) simulations, and in silico screening of compounds against the cyclin D/CDK axis. Initial MD simulations examine the binding mechanism of palbociclib, a known CDK4 inhibitor while docking studies screen diverse compound libraries to identify potential therapeutics. The outcomes are expected to guide lead optimization and the development of promising cyclin D/CDK axis inhibitors, offering novel avenues for cancer treatment.