Proteomic Analysis Reveals Trilaciclib-Induced Senescence

Abstract

ABSTRACTTrilaciclib, a CDK4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer (ES-SCLC). This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in haematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in haematological cancers. Utilizing mass spectrometry-based proteomics, we examined the alterations induced by trilaciclib in the chronic myeloid leukaemia (CML) cell line, K562. Interestingly, trilaciclib promoted senescence in these cells rather than cell death, as observed in acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), and myeloma cells. In K562 cells, trilaciclib hindered cell cycle progression and proliferation by stabilising CDK4/6 and downregulating cell cycle-related proteins, along with the concomitant activation of autophagy pathways. Additionally, trilaciclib-induced senescence was also observed in the non-small cell lung carcinoma cell line (NSCLC), A549. These findings highlight trilaciclib’s potential as a therapeutic option for haematological cancers and underscore the need to carefully balance senescence induction and autophagy modulation in CML treatment, as well as in NSCLC.ABSTRACT GRAPHIC