VP79s Synergistically Enhances Venetoclax Activity in Multiple Myeloma Cells, Overcoming Drug Resistance

Multiple myeloma (MM) remains an incurable plasma cell malignancy, with most patients experiencing relapse or becoming refractory to current treatments. This persistent challenge stems from the disease's inherent heterogeneity and the protective effects of the bone marrow (BM) microenvironment, which fosters drug resistance. Novel therapeutic strategies are urgently needed to overcome these limitations. VP79s, a novel guanidinium-based compound, has previously demonstrated potent anti-myeloma activity by targeting the dysregulated IL-6/JAK/STAT signalling pathway, a critical driver of MM cell survival and proliferation. This study explores its potential to synergize with the BH3 mimetic venetoclax, which targets Bcl-2 family proteins, to address the complex mechanisms of MM drug resistance.