DOI: 10.1182/blood.v96.9.2943. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy

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

10.1182/blood.v96.9.2943

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

AbstractAlthough 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.

Bibliography

Hideshima, T., Chauhan, D., Shima, Y., Raje, N., Davies, F. E., Tai, Y.-T., Treon, S. P., Lin, B., Schlossman, R. L., Richardson, P., Muller, G., Stirling, D. I., & Anderson, K. C. (2000). Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood, 96(9), 2943â2950.

Authors 13

Teru Hideshima (first)
Dharminder Chauhan (additional)
Yoshihito Shima (additional)
Noopur Raje (additional)
Faith E. Davies (additional)
Yu-Tzu Tai (additional)
Steven P. Treon (additional)
Boris Lin (additional)
Robert L. Schlossman (additional)
Paul Richardson (additional)
George Muller (additional)
David I. Stirling (additional)
Kenneth C. Anderson (additional)

References 31 Referenced 673

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Dates

Type	When
Created	5 years, 10 months ago (Oct. 13, 2019, 10:54 p.m.)
Deposited	1 year, 11 months ago (Sept. 21, 2023, 12:04 p.m.)
Indexed	1 month ago (Aug. 2, 2025, 1:24 a.m.)
Issued	24 years, 10 months ago (Nov. 1, 2000)
Published	24 years, 10 months ago (Nov. 1, 2000)
Published Print	24 years, 10 months ago (Nov. 1, 2000)

Funders 0

None

BibTeX

@article{Hideshima_2000, title={Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy}, volume={96}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v96.9.2943}, DOI={10.1182/blood.v96.9.2943}, number={9}, journal={Blood}, publisher={American Society of Hematology}, author={Hideshima, Teru and Chauhan, Dharminder and Shima, Yoshihito and Raje, Noopur and Davies, Faith E. and Tai, Yu-Tzu and Treon, Steven P. and Lin, Boris and Schlossman, Robert L. and Richardson, Paul and Muller, George and Stirling, David I. and Anderson, Kenneth C.}, year={2000}, month=nov, pages={2943–2950} }

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