Actionable Strategies to Target Multiple Myeloma Plasma Cell Resistance/Resilience to Stress: Insights From “Omics” Research

While the modern therapeutic armamentarium to treat multiple myeloma (MM) patients allows a longer control of the disease, this second-most-frequent hematologic cancer is still uncurable in the vast majority of cases. Since MM plasma cells are subjected to various types of chronic cellular stress and the integrity of specific stress-coping pathways is essential to ensure MM cell survival, not surprisingly the most efficacious anti-MM therapy are those that make use of proteasome inhibitors and/or immunomodulatory drugs, which target the biochemical mechanisms of stress management. Based on this notion, the recently realized discoveries on MM pathobiology through high-throughput techniques (genomic, transcriptomic, and other “omics”), in order for them to be clinically useful, should be elaborated to identify novel vulnerabilities in this disease. This groundwork of information will likely allow the design of novel therapies against targetable molecules/pathways, in an unprecedented opportunity to change the management of MM according to the principle of “precision medicine.” In this review, we will discuss some examples of therapeutically actionable molecules and pathways related to the regulation of cellular fitness and stress resistance in M