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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
A virtual approach to evaluate therapies for management of multiple myeloma induced bone disease
Bing Ji1, Paul G Genever2, Michael J Fagan3
1School of Control Science and Engineering, Shandong University, Jinan, 250061, People's Republic of China.
Abstract:
Multiple myeloma bone disease is devastating for patients and a major cause of morbidity. The disease leads to bone destruction by inhibiting osteoblast activity while stimulating osteoclast activity. Recent advances in multiple myeloma research have improved our understanding of the pathogenesis of multiple myeloma-induced bone disease and suggest several potential therapeutic strategies. However, the effectiveness of some potential therapeutic strategies still requires further investigation and optimization. In this paper, a recently developed mathematical model is extended to mimic and then evaluate three therapies of the disease, namely: bisphosphonates, bortezomib and TGF-β inhibition. The model suggests that bisphosphonates and bortezomib treatments not only inhibit bone destruction, but also reduce the viability of myeloma cells. This contributes to the current debate as to whether bisphosphonate therapy has an anti-tumour effect. On the other hand, the analyses indicate that treatments designed to inhibit TGF-β do not reduce bone destruction, although it appears that they might reduce the viability of myeloma cells, which again contributes to the current controversy regarding the efficacy of TGF-β inhibition in multiple myeloma-induced bone disease.
Insights
This study uses a mathematical model to evaluate multiple myeloma bone disease therapies. Bisphosphonates and bortezomib show promise in inhibiting bone destruction and reducing myeloma cell viability, unlike TGF-β inhibition.
Area of Science:
- Oncology
- Biomathematics
- Skeletal Biology
Background:
- Multiple myeloma bone disease causes significant patient morbidity by disrupting bone remodeling.
- Current understanding of disease pathogenesis is advancing, but therapeutic strategies require further validation.
Purpose of the Study:
- To extend a mathematical model to simulate and assess the efficacy of three distinct therapeutic strategies for multiple myeloma-induced bone disease.
- To evaluate bisphosphonates, bortezomib, and TGF-β inhibition using a computational approach.
Main Methods:
- Development and application of an extended mathematical model.
- Simulation of bisphosphonate therapy.
- Simulation of bortezomib therapy.
- Simulation of TGF-β inhibition therapy.
Main Results:
- The model predicts that bisphosphonates and bortezomib inhibit bone destruction and decrease myeloma cell viability, supporting their anti-tumor effects.
- TGF-β inhibition did not appear to reduce bone destruction in the model, but may reduce myeloma cell viability, contributing to ongoing debate.
Conclusions:
- Bisphosphonates and bortezomib show potential for dual action against bone disease and myeloma cells.
- The efficacy of TGF-β inhibition for multiple myeloma-induced bone disease remains controversial and warrants further investigation.
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