Evaluation of molecular mechanisms of resistance to proteasome inhibitors and immunomodulatory drugs in multiple myeloma

Overview

Project Summary

Multiple myeloma (MM) is characterized by abnormal proliferation of monoclonal plasma cells producing monoclonal immunoglobulins. Current therapies, including proteasome inhibitors (bortezomib, carfilzomib, ixazomib), immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide), and monoclonal antibodies (daratumumab), have improved outcomes but the disease remains incurable due to clonal heterogeneity leading to drug resistance. Resistance to proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) is complex and multifactorial, involving factors like clonal evolution, cancer stem cells, and changes in the bone marrow microenvironment.

Main Goals

This project aims to investigate molecular mechanisms involved in PIs and IMiDs resistance, focusing on the role of drug metabolism genes, proteasome activator complex subunits, cereblon expression, and NRF2 and NF-KB pathways.

Project Details