Table 1.
Summary of selected research evaluating potential biomarkers associated with bortezomib resistant multiple myeloma.
| Author | Title | Result |
|---|---|---|
| Stessman et al, 2013 | Bortezomib resistance can be reversed by induced expression of plasma cell maturation markers in a mouse in vitro model of multiple myeloma | Certain genes were identified as biomarkers and may indicate a mechanism for Bz resistance through the loss of PC maturation. Induced PC maturation in both acquired and innate resistant cells restored Bz sensitivity |
| Stessman et al, 2013 | Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model | Identified 23 gene signature that distinguished between BzS and BzR mouse cell lines and significantly predicted differences in patient outcomes in a clinical trial utilizing Bz |
| Stessman et al, 2013 | Reduced CXCR4 expression is associated with extramedullary disease in a mouse model of myeloma and predicts poor survival in multiple myeloma patients treated with bortezomib | Determined that low CXCR4 is associated with Bz resistance and poor outcomes. Supports the use of CXCR4 as a diagnostic biomarker that predicts clinical outcome in patients treated with Bz |
| Ri et al, 2010 | Bortezomib-resistant myeloma cell lines: a role for mutated PSMB5 in preventing the accumulation of unfolded proteins and fatal ER stress | Preventing the accumulation of misfolded proteins and avoidance of ER stress has an important role in Bz resistance by suppressing apoptosis-inducing signals in MM cells |
| Agnelli et al, 2011 | The reconstruction of transcriptional networks reveals critical genes with implications for clinical outcome of multiple myeloma | Gene signatures demonstrated to predict survival were determined utilizing data from 7 MM datasets |
| Zhu et al, 2011 | RNAi screen of the druggable genome identifies modulators of proteasome inhibitor sensitivity in myeloma including CDK5 | Identified 37 genes which when silenced are not directly cytotoxic but do synergistically promote inhibitory effects of Bz. Combinations of Bz with other proteasome inhibitor drugs or combinations with inhibitors of CDK5 make sense to explore for response prediction |
| Fernandez de Larrea et al, 2013 | Impact of global and gene-specific DNA methylation pattern in relapsed multiple myeloma patients treated with bortezomib | Combination of highly methylated global genome with low NFkB1 methylation status defined a specific subset of patients with better prognosis |
| Kaiser et al, 2013 | Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma | Assessment of DNA methylation of certain genes could provide a clinically useful tool for risk determination and individualized treatment selection in MM |
| Lohr et al, 2014 | Widespread genetic heterogeneity in multiple myeloma: Implications for targeted therapy | Heterogeneity analysis displays clinical utility for treatment decisions |
| Bolli et al, 2013 | Heterogeneity of genomic evolution and mutational profiles in multiple myeloma | The heterogeneity of the MM genome may impact prognosis stratification treatment approach and assessment of treatment response |