Proteomic Analysis Reveals Trilaciclib-Induced Senescence
Trilaciclib, a cyclin-dependent kinase 4/6 inhibitor, has been approved as a myeloprotective agent to shield bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer. This effect is achieved by temporarily halting the cell cycle of bone marrow cells. While trilaciclib has been studied in various cancer types, its potential in hematological malignancies has yet to be fully explored. This study aimed to evaluate the efficacy of trilaciclib in hematological cancers. Using mass spectrometry-based proteomics, we analyzed the cellular changes induced by trilaciclib in the chronic myeloid leukemia cell line K562. Surprisingly, rather than inducing cell death, as observed in acute myeloid leukemia, acute lymphoblastic leukemia, and myeloma cells, trilaciclib primarily induced senescence in K562 cells. In these cells, trilaciclib inhibited cell cycle progression and proliferation by stabilizing cyclin-dependent kinases 4/6, downregulating cell cycle-related proteins, and activating autophagy pathways. Additionally, senescence induction was also observed in the nonsmall cell lung carcinoma cell line A549. These findings suggest that trilaciclib may offer therapeutic potential for hematological cancers, highlighting the importance of carefully balancing senescence induction and autophagy modulation in the treatment of chronic myeloid leukemia and nonsmall cell lung carcinoma.