Advanced progressive dedifferentiated liposarcoma (DDLS) tumors frequently harbor copy number alterations in chromosome 12q, which encompasses CDK4. Phase II clinical trials assessing CDK4/6 inhibitors have shown modest success in extending progression-free survival (PFS) in patients with liposarcoma, potentially by inducing cell senescence or enhancing antigen presentation in tumor cells. In this phase II trial, Gleason and colleagues evaluate the efficacy of the CDK4/6 inhibitor abemaciclib in patients with DDLS and investigate the mechanism by which abemaciclib exerts its antitumoral effects. The authors note a median PFS of 33 weeks, with 76.7% of patients progression-free at 12 weeks and no new adverse events. Additional preclinical work in liposarcoma cell lines identified ANGPTL4 as a regulator of cell progression from quiescence to senescence and inflammation. The authors found that senescence modulates the immune tumor microenvironment as demonstrated by an increase in CD4+ leukocyte infiltration, yet patients with both senescence and...

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