Br J Cancer: An alternative strategy for reversing drug resistance to multiple myeloma

Protease inhibitors (PIs) can significantly improve the treatment response to multiple myeloma (MM) and improve patient survival.
, resistance in PI treatment remains a major obstacle to the treatment of the disease.
may be caused by genetic mutations, but more and more evidence highlights the role of non-mutant preceptogenetic mechanisms.
, changes in the appearance of genetics also involve the loss of drug resistance.
, however, very little research has been made on the mechanism of PI resistance, especially the role of epigenetic regulation in the occurrence and elimination of PI resistance.
An epigenetic regulatory model that produces and eliminates PI tolerance in MM cells this study assesses the epigenetic regulatory factors of the disorder by analyzing resistance in relapsed MM patients, MM cell line, and mouse models of bortezomib.
further to the cells resistant to PI and the efficacy of the drug through internal and external experiments.
reversible PI tolerance is mediated by epigenetic changes researchers have found that after PI treatment, MM cells enter a slow-cycle and reversible drug-to-tolerance state.
this reversible state is associated with the plasticity of the observational genetics, which involves tolerance rather than persistence in patients with MM recurrence.
contrary to persistent PI single-drug therapy, a combined treatment of histone deacetylase inhibitors and high-dose intermittent therapy can treat MM more effectively by preventing the emergence of PI-resistant cells.
treatment is mainly achieved by reversing the imbalance of the relevant surface genetic regulatory factors in MM patients.
, the study suggests another mechanism for the development of non-mutant PI resistance, which also explains why PI recurrence is inevitable and why patients regain sensitivity after "dosing day."
the study also proposed a strategy for the elimination of drug-resistant cells by the observational genetics.
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