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Updated: Jan 26, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Targeting transcription factors in multiple myeloma: evolving therapeutic strategies
Shirong Li1, Sonia Vallet2, Antonio Sacco3
1a Division of Hematology/Oncology , Columbia University , New York , NY , USA.
Introduction:
Transcription factors (TFs) are convergence points of signaling cascades that coordinate cell differentiation, proliferation, survival, and migration; and are commonly deregulated in solid and hematologic malignancies, including multiple myeloma (MM). Several recent studies indicate that the inhibition of TFs may lead to selective tumor cell death with little or no consequences for normal cells due to redundancy in signaling pathways. Nuclear hormone receptor (NHR)- TFs belong to the most common therapies in oncology today. In contrast, non-NHR-TFs have been considered 'un- druggable' until most recently.
Areas Covered:
This review article summarizes advances of our knowledge on the complex composition of non-NHR-TFs and their binding to cognate DNA sequences that are propelling the development of novel strategies in MM.
Expert Opinion:
Protein-protein and protein-DNA- binding inhibitors, proteolysis- targeting chimeric molecules, and chromatin remodeling/epigenetic reader inhibitors are among the most promising novel compounds with a potentially high therapeutic index; they are likely to once more advance MM treatment strategies and improve patient outcome in the near future.
Insights
Targeting transcription factors (TFs) offers new hope for multiple myeloma (MM). Non-nuclear hormone receptor (NHR)-TFs, once undruggable, are now targets for novel MM therapies, improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Transcription factors (TFs) regulate critical cellular processes and are frequently altered in cancers like multiple myeloma (MM).
- Nuclear hormone receptor (NHR)-TFs are established oncology targets, while non-NHR-TFs were historically considered undruggable.
- Targeting TFs can induce selective cancer cell death due to pathway redundancy in normal cells.
Purpose of the Study:
- To review the complex composition of non-NHR-TFs.
- To explore their DNA-binding mechanisms.
- To highlight novel therapeutic strategies for MM based on non-NHR-TF targeting.
Main Methods:
- Literature review of recent studies on non-NHR-TFs in MM.
- Analysis of TF-DNA binding interactions.
- Summary of emerging therapeutic approaches.
Main Results:
- Non-NHR-TFs represent a promising class of targets in MM.
- Novel compounds like protein-protein/DNA-binding inhibitors and proteolysis-targeting chimeras are advancing MM treatment.
- Chromatin remodeling and epigenetic reader inhibitors show therapeutic potential.
Conclusions:
- Targeting non-NHR-TFs is a rapidly evolving area with significant potential for MM treatment.
- These novel strategies offer a high therapeutic index and are expected to improve patient outcomes.
- Advances in understanding TF complexes and DNA binding are driving these new therapeutic developments.
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