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Updated: Nov 21, 2025

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
09:41

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells

Published on: July 15, 2015

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Treatment Strategies Considering Micro-Environment and Clonal Evolution in Multiple Myeloma

Kazuhito Suzuki1,2, Kaichi Nishiwaki1,2, Shingo Yano2

  • 1Division of Clinical Oncology/Hematology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, Kashiwa-shita 163-1, Kashiwa-city, Chiba 277-8567, Japan.

Cancers
|January 13, 2021
PubMed

Insights

Multiple myeloma drug resistance stems from the tumor microenvironment and clonal evolution. Early treatment with proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and stem cell transplant is crucial for overcoming resistance.

Area of Science:

  • Hematological Malignancies
  • Cancer Drug Resistance
  • Tumor Microenvironment Dynamics

Background:

  • Multiple myeloma is an incurable blood cancer characterized by acquired drug resistance.
  • De novo resistance arises from the tumor microenvironment (e.g., cell adhesion, cytokines, hypoxia).
  • Acquired resistance is driven by clonal evolution (branching, linear, neutral).

Purpose of the Study:

  • To review the role of anti-myeloma agents in modulating the microenvironment and clonal evolution.
  • To summarize treatment strategies for overcoming drug resistance in multiple myeloma.
  • To highlight the importance of initial treatment combinations.

Main Methods:

  • Review of scientific literature on multiple myeloma pathogenesis and treatment.
  • Analysis of mechanisms of de novo and acquired drug resistance.
  • Evaluation of therapeutic agents targeting the myeloma microenvironment and clonal evolution.

Main Results:

  • The tumor microenvironment and clonal evolution are key drivers of multiple myeloma drug resistance.
  • Proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and ASCT improve prognosis by targeting the microenvironment.
  • Branching evolution depends on the microenvironment, while linear/neutral evolution correlates with poor prognosis.

Conclusions:

  • Effective treatment strategies must address both de novo and acquired drug resistance.
  • Initial therapy incorporating proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and ASCT is vital.
  • Understanding microenvironmental and evolutionary factors is critical for improving multiple myeloma outcomes.
Keywords:
anti-CD38 monoclonal antibodyautologous stem cell transplantationbone marrow nichebone marrow stromal cellclonal evolutiondrug resistanceimmunomodulatory drugsmultiple myelomaproteasome inhibitors

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