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The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease. | LitMetric

AI Article Synopsis

  • Multiple myeloma (MM) is a type of cancer that attacks the bones and is hard to cure because it can become resistant to treatments.
  • Researchers created a special computer model to study how MM cancer cells change and survive in the bone environment.
  • The model shows that protecting cells in the bone can help some cancer cells survive treatment, but targeting these protective effects could help make treatments work better and delay the disease from coming back.

Article Abstract

Multiple myeloma (MM) is an osteolytic malignancy that is incurable due to the emergence of treatment resistant disease. Defining how, when and where myeloma cell intrinsic and extrinsic bone microenvironmental mechanisms cause relapse is challenging with current biological approaches. Here, we report a biology-driven spatiotemporal hybrid agent-based model of the MM-bone microenvironment. Results indicate MM intrinsic mechanisms drive the evolution of treatment resistant disease but that the protective effects of bone microenvironment mediated drug resistance (EMDR) significantly enhances the probability and heterogeneity of resistant clones arising under treatment. Further, the model predicts that targeting of EMDR deepens therapy response by eliminating sensitive clones proximal to stroma and bone, a finding supported by in vivo studies. Altogether, our model allows for the study of MM clonal evolution over time in the bone microenvironment and will be beneficial for optimizing treatment efficacy so as to significantly delay disease relapse.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951361PMC
http://dx.doi.org/10.1038/s41467-024-46594-0DOI Listing

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