Research Progress on Molecular Mechanisms of Resistance to Bortezomib in Multiple Myeloma- Review / 中国实验血液学杂志

ABSTRACT

Over the last decade, bortezomib(BTZ) has been extensively applied in the treatment of hematological malignancies, particularly in multiple myeloma and mantle cell lymphoma, however, the appearence of secondary resistance to BTZ has brought a huge challenge in MM treatment. In the present review, the mechanisms of resistance to bortezomib in MM are summarized, focusing on the action of ubiquitin-proteasome system(UPS), endoplasmin reticulum stress, antophagy, inducible pro-survival signalling and bone marrow microenvironment as well as exploration of the potential therapeutic strategies in the clinical perspective. With the understanding of the molecular mechanisms for resistance to BTZ, the novel histone deacetylase inhibitors(HDACi) have been approved for the treatment of replased/refractory MM and AKT inhibitor in the clinical trials. These novel combined therapies can enhance BTZ efficiency and improve the outcome of the patients.