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This combination therapy pairs palbociclib, a selective small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), with tislelizumab, a humanized IgG4 monoclonal antibody targeting the programmed cell death protein 1 (PD-1) receptor. Developed as a collaborative investigation by Sun Yat-sen Memorial Hospital and Sun Yat-sen University, the regimen is primarily being evaluated for the treatment of locally advanced or metastatic bladder urothelial carcinoma. Palbociclib functions by inducing G1 phase cell cycle arrest, which not only inhibits tumor cell proliferation but also potentially enhances the immune microenvironment by increasing tumor antigen presentation. Tislelizumab complements this by blocking the PD-1/PD-L1 pathway, thereby preventing T-cell exhaustion and restoring the body's natural anti-tumor immune response. The combination aims to leverage these synergistic mechanisms to overcome resistance to monotherapy and improve clinical outcomes in patients with advanced urothelial malignancies.
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