Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy

DOI PDF 21 Citations
  • Teru Hideshima
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • Dharminder Chauhan
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • Yoshihito Shima
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • Noopur Raje
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • Faith E. Davies
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • Yu-Tzu Tai
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • Steven P. Treon
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • Boris Lin
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • Robert L. Schlossman
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • Paul Richardson
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • George Muller
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • David I. Stirling
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.
  • Kenneth C. Anderson
    From the Department of Adult Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA; and Celgene Corporation, Warren, NJ.

Bibliographic Information

Published
2000-11-01
DOI
  • 10.1182/blood.v96.9.2943
Publisher
American Society of Hematology

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Description

<jats:title>Abstract</jats:title><jats:p>Although thalidomide (Thal) was initially used to treat multiple myeloma (MM) because of its known antiangiogenic effects, the mechanism of its anti-MM activity is unclear. These studies demonstrate clinical activity of Thal against MM that is refractory to conventional therapy and delineate mechanisms of anti-tumor activity of Thal and its potent analogs (immunomodulatory drugs [IMiDs]). Importantly, these agents act directly, by inducing apoptosis or G1 growth arrest, in MM cell lines and in patient MM cells that are resistant to melphalan, doxorubicin, and dexamethasone (Dex). Moreover, Thal and the IMiDs enhance the anti-MM activity of Dex and, conversely, are inhibited by interleukin 6. As for Dex, apoptotic signaling triggered by Thal and the IMiDs is associated with activation of related adhesion focal tyrosine kinase. These studies establish the framework for the development and testing of Thal and the IMiDs in a new treatment paradigm to target both the tumor cell and the microenvironment, overcome classical drug resistance, and achieve improved outcome in this presently incurable disease.</jats:p>

Journal

  • Blood

    Blood 96 (9), 2943-2950, 2000-11-01

    American Society of Hematology

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