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Updated: May 4, 2026
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms
Jahangir Abdi1, Guoan Chen, Hong Chang
1Dept. of Laboratory Medicine & Pathobiology, University of Toronto, Ontario, Canada.
Abstract:
In the era of new and mostly effective therapeutic protocols, multiple myeloma still tends to be a hard-to-treat hematologic cancer. This hallmark of the disease is in fact a sequel to drug resistant phenotypes persisting initially or emerging in the course of treatment. Furthermore, the heterogeneous nature of multiple myeloma makes treating patients with the same drug challenging because finding a drugable oncogenic process common to all patients is not yet feasible, while our current knowledge of genetic/epigenetic basis of multiple myeloma pathogenesis is outstanding. Nonetheless, bone marrow microenvironment components are well known as playing critical roles in myeloma tumor cell survival and environment-mediated drug resistance happening most possibly in all myeloma patients. Generally speaking, however; real mechanisms underlying drug resistance in multiple myeloma are not completely understood. The present review will discuss the latest findings and concepts in this regard. It reviews the association of important chromosomal translocations, oncogenes (e.g. TP53) mutations and deranged signaling pathways (e.g. NFκB) with drug response in clinical and experimental investigations. It will also highlight how bone marrow microenvironment signals (Wnt, Notch) and myeloma cancer stem cells could contribute to drug resistance in multiple myeloma.
Insights
Multiple myeloma remains challenging due to drug resistance. This review explores genetic mutations, signaling pathways, and the bone marrow microenvironment
Area of Science:
- Hematologic Oncology
- Cancer Biology
- Drug Resistance Mechanisms
Background:
- Multiple myeloma is a challenging hematologic cancer despite new therapies.
- Drug resistance, either intrinsic or acquired, is a hallmark of this disease.
- Tumor heterogeneity complicates treatment strategies.
Purpose of the Study:
- To review the latest findings on drug resistance mechanisms in multiple myeloma.
- To discuss the role of genetic alterations and signaling pathways in treatment response.
- To highlight the contribution of the bone marrow microenvironment and cancer stem cells to drug resistance.
Main Methods:
- Review of clinical and experimental investigations.
- Analysis of associations between genetic factors and drug response.
- Exploration of bone marrow microenvironment signals and cancer stem cell roles.
Main Results:
- Drug resistance is linked to chromosomal translocations, oncogene mutations (e.g., TP53), and aberrant signaling pathways (e.g., NFκB).
- Bone marrow microenvironment signals (Wnt, Notch) are implicated in myeloma cell survival and drug resistance.
- Myeloma cancer stem cells may also contribute to therapeutic challenges.
Conclusions:
- Understanding the complex mechanisms of drug resistance is crucial for improving multiple myeloma treatment.
- Targeting genetic factors, signaling pathways, and the tumor microenvironment holds therapeutic potential.
- Further research into cancer stem cells is needed to overcome treatment resistance.
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