Fig. 4: Schematic model of epigenetic regulation in the generation and elimination of PI tolerance in MM cells. | British Journal of Cancer

Fig. 4: Schematic model of epigenetic regulation in the generation and elimination of PI tolerance in MM cells.

From: Modulating proteasome inhibitor tolerance in multiple myeloma: an alternative strategy to reverse inevitable resistance

Fig. 4: Schematic model of epigenetic regulation in the generation and elimination of PI tolerance in MM cells.

PI treatment induced MM cells to enter epigenetic alteration-mediated reversible tolerance. Exposure to further chemotherapy and selection can ‘lock in’ an epigenetic state, resulting in proliferation of a hardwired drug-resistant population. However, combination with HDAC inhibitors (HDACis) and high-dosage intermittent therapy can reverse epigenetic tolerance and prevent the emergence of PI-tolerant cells. TME tumour microenvironment, ECM extracellular matrix.

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