Co-targeting CDK4 and MDM2 in Liposarcoma using Novel Dual-Target Inhibitors

Liposarcoma, a malignant soft tissue sarcoma, is frequently characterized by MDM2 amplification and CDK4 overexpression, making these proteins attractive therapeutic targets. Current treatments utilize MDM2 or CDK4 inhibitors seperately, but face challenges such as resistance and limited efficacy. This study evaluates the therapeutic potential of novel dual- target inhibitors that simultaneously suppress MDM2 and CDK4 in an in vitro liposarcoma model. Cytotoxicity and dose-response experiments are performed to determine IC50 values, assess cell viability, and establish optimal therapeutic concentrations. The novel compounds are directly compared to FDA-approved monotherapies, abemaciclib and idasanutlin, that selectively inhibit MDM2 or CDK4, both individually and in combination. Proteomics and transcriptional profiling are then used to investigate the further effects of each treatment on the cell progression and downstream effects of apoptosis. By comparing the efficacy of dual inhibition to conventional monotherapies, this study aims to determine whether co-targeting MDM2 and CDK4 offers a more effective therapeutic approach. These findings may provide insights into the development of improved treatment strategies for liposarcoma and other cancers driven by MDM2 and CDK4 dysregulation.