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Updated: Jan 16, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Computational Drug Repurposing Across the Multiple Myeloma Spectrum: From MGUS to MM
Kyriaki Savva1, Marilena M Bourdakou1, Dimitris Stellas2
1Bioinformatics Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus.
Background/Objectives:
Multiple myeloma (MM) is a challenging, B cell malignancy characterised by the uncontrolled proliferation of plasma cells within the bone marrow. Despite significant advances in treatment options nowadays, MM remains an incurable malignancy, with the majority of patients succumbing to the disease. MM develops from a pre-malignant state known as monoclonal gammopathy of unknown significance (MGUS), which then has the potential to evolve either into smouldering (asymptomatic) multiple myeloma (SMM) or into MM. Since novel drug discovery takes years to reach the clinic, drug repurposing, which concerns the detection of existing drugs for a novel disease, can be applied.
Methods:
To address this critical and still unmet medical need, we present a comprehensive signature-based drug-repurposing approach using all the publicly available bulk transcriptomics datasets on mGUS, sMM, and MM.
Results:
Our study included an in-house scoring scheme approach enabling further filtering and prioritisation, resulting in 25 candidate repurposed drugs for mGUS, 23 for sMM, and 66 for MM. The corresponding gene targets and the related functional terms have been analysed, providing extra information for stage-specific underlying mechanisms in myeloma. Lastly, enabled by a specific computational workflow, we propose drug combinations between our top candidate repurposed drugs and FDA-approved drugs for MM.
Conclusions:
Together, these results deliver a stage-specific, transparent resource for MM drug repurposing and combination design, intended to accelerate translation toward earlier disease intervention and improved patient outcomes.
Insights
This study identifies potential repurposed drugs for multiple myeloma (MM) and its precursor stages, monoclonal gammopathy of unknown significance (MGUS) and smouldering multiple myeloma (SMM). The findings aim to accelerate new treatments for these B cell malignancies.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Multiple myeloma (MM) is an incurable B cell malignancy originating from monoclonal gammopathy of unknown significance (MGUS) and progressing through smouldering multiple myeloma (SMM).
- Despite treatment advances, MM remains a significant unmet medical need, driving the search for novel therapeutic strategies.
- Drug repurposing offers a faster route to clinical application compared to de novo drug discovery.
Purpose of the Study:
- To identify existing drugs that can be repurposed for treating different stages of multiple myeloma (MM), including its precursor conditions.
- To develop a stage-specific drug repurposing strategy for MM using transcriptomics data.
- To propose novel drug combinations for MM treatment.
Main Methods:
- A comprehensive signature-based drug repurposing approach was employed, utilizing all publicly available bulk transcriptomics datasets for MGUS, SMM, and MM.
- An in-house scoring scheme was developed for filtering and prioritizing candidate repurposed drugs.
- A computational workflow was used to identify potential drug combinations with FDA-approved MM therapies.
Main Results:
- The study identified 25 candidate repurposed drugs for MGUS, 23 for SMM, and 66 for MM.
- Gene targets and functional terms were analyzed to provide insights into stage-specific mechanisms of myeloma.
- Potential drug combinations were proposed, integrating repurposed candidates with existing MM treatments.
Conclusions:
- The developed resource offers a stage-specific and transparent approach to drug repurposing and combination design for MM.
- These findings are intended to accelerate the translation of research into clinical practice for earlier MM intervention.
- The study aims to improve patient outcomes by providing novel therapeutic avenues for multiple myeloma and its precursor stages.
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