Thalidomide And Its Analogs Overcome Drug Resistance Of Human Multiple Myeloma Cells To Conventional Therapy.
Teru Hideshima, Dharminder Chauhan, Yoichiro Shima, Noopur Raje, Faith Davies, Yonghua Tai, Steven P Treon, Boris Lin, Robert L. Schlossman, Paul G Richardson, G Muller, David I. Stirling, K C Anderson
Published 2000 · Medicine
Download PDFAnalyze on Scholarcy
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.
This paper references
Resistance to Apoptosis Conferred by Cdk Inhibitors During Myocyte Differentiation
Jing Feng Wang (1996)
Expression of vascular endothelial growth factor and its receptor in hematological malignancies
W Bellamy (1999)
Multiple myeloma: increasing evidence for a multistep transformation process.
Michael Hallek (1998)
Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade.
Henry Geitz (1996)
Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity
Toufan Parman (1999)
Isolation and characterization of human multiple myeloma cell enriched populations.
Yuanyuan Tai (2000)
The influence of thalidomide on the clinical and immunologic manifestation of erythema nodosum leprosum.
Elizabeth Pereira Sampaio (1993)
Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells.
Dharminder Chauhan (1997)
Genetic determinants of p53-induced apoptosis and growth arrest.
Kornelia Polyak (1996)
Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines.
Jason S. Damiano (1999)
pression of vascular endothelial growth factor and its receptor in hematological malignancies
W Bellamy (1999)
Characterization of signaling cascades triggered by human interleukin-6 versus Kaposi's sarcoma-associated herpes virus-encoded viral interleukin 6.
Teru Hideshima (2000)
Cytochrome c-dependent and -independent Induction of Apoptosis in Multiple Myeloma Cells*
Dharminder Chauhan (1997)
Anti-tumor activity of thalidomide in refractory multiple myeloma
S Singhal (1999)
CD40 ligand triggered interleukin-6 secretion in multiple myeloma.
Mitsuyoshi Urashima (1995)
lidomide costimulates primary human T lymphocytes , preferentially inducing proliferation , cytokine production , and cytotoxic responses in the CD 8 1 subset
Haslett PAJ (1998)
Adhesion of human myelomaderived cell lines to bone marrow stromal cells stimulates IL-6 secretion
H Uchiyama (1993)
Thalidomide--a revival story.
Nishita Raje (1999)
Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma.
Angelo Vacca (1999)
Blockade of mitogen-activated protein kinase cascade signaling in interleukin 6-independent multiple myeloma cells.
Atsushi Ogata (1997)
Thalidomide Costimulates Primary Human T Lymphocytes, Preferentially Inducing Proliferation, Cytokine Production, and Cytotoxic Responses in the CD8+ Subset
Patrick A. J. Haslett (1998)
Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B.
Dharminder Chauhan (1996)
Thalidomide is an inhibitor of angiogenesis.
Robert J D'Amato (1994)
Thalidomide: Therapeutic potential in hematologic malignancies
Kenneth C. Anderson (2000)
Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma
Domenico Ribatti (1999)
Thalidomide on the comeback trail
Barbara F. Hales (1999)
Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha.
Laura G. Corral (1999)
RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells
Dharminder Chauhan (1999)
Interleukin-6 Overcomes p21WAF1 Upregulation and G1 Growth Arrest Induced by Dexamethasone and Interferon-γ in Multiple Myeloma Cells
Mitsuyoshi Urashima (1997)
tiple myeloma cell adhesion - induced interleukin - 6 expression in bone marrow stromal cells involves activation of NFk B
D Chauhan (1996)
Response of purified myeloma cells to hematopoietic growth factors
KC Anderson (1924)
Interleukin-6 triggers cell growth via the ras-dependent mitogen-activated protein kinase cascade
A Ogata (1997)
Dexamethasone induces apoptosis of multiple myeloma cells in a JNK/SAP kinase independent mechanism
Dharminder Chauhan (1997)
This paper is referenced by
Updates to the guidelines for the diagnosis and management of multiple myeloma.
Guy Pratt (2014)
Thalidomide Embryopathy - Orthopaedic aspects. Degenerative changes and quality of life at age 45
Shadi-Afarin Ghassemi Jahani (2016)
Polymorphisms of CYP2C19 gene are associated with the efficacy of thalidomide-based regimens in multiple myeloma
Yonghua Li (2007)
Patupilone (epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo.
Boris Lin (2005)
Targeting signalling pathways for the treatment of multiple myeloma
Klaus Podar (2005)
A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma.
Paul G Richardson (2006)
A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed/refractory multiple myeloma
James R. Berenson (2012)
Evaluation of antiproliferative effect of N-(alkyladamantyl)phthalimides in vitro.
Margareta Horvat (2012)
Novel lenalidomide-based combinations for treatment of multiple myeloma.
Mauro Cives (2013)
study of 169 patients single-agent thalidomide: identification of prognostic factors in a phase 2 Extended survival in advanced and refractory multiple myeloma after
Maurizio Zangari (2013)
Thalidomide inhibits interferon-γ-mediated nitric oxide production in mouse vascular endothelial cells.
Battuvshin Badamtseren (2011)
Concluding remarks and future directions.
Jesús F. San-Miguel (2010)
Lenalidomide in multiple myeloma
Bhawna Sirohi (2009)
Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation.
Shoso Munemasa (2008)
well tolerated in patients with relapsed multiple myeloma Immunomodulatory drug CC-5013 overcomes drug resistance and is
Kathe Balinski (2013)
New immune modulators
Loredana Santo (2013)
Isosteric analogs of lenalidomide and pomalidomide: synthesis and biological activity.
Alexander L. Ruchelman (2013)
Thalidomide plus oral melphalan for advanced multiple myeloma: a phase II study.
Massimo Offidani (2003)
CARATTERIZZAZIONE CITOGENETICO- MOLECOLARE IN PAZIENTI CON MIELOMA MULTIPLO. IMPLICAZIONI PROGNOSTICHE DELLE DELEZIONI DEL CROMOSOMA 13 E DEL CROMOSOMA 17
Stefano A. Pileri (2006)
Immune parameters in multiple myeloma patients: influence of treatment and correlation with opportunistic infections
Philipp Schuett (2006)
An update on current and prospective immunotherapies for chronic lymphocytic leukemia.
Josephine Emole (2015)
Arsenic Trioxide in Multiple Myeloma: Rationale and Future Directions
Kenneth C. Anderson (2002)
Lenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in Multiple Myeloma
Güllü T Görgün (2015)
Clarithromycin Synergistically Enhances Thalidomide Cytotoxicity in Myeloma Cells
Xu-Hua Qiu (2015)
Current advances in non-proteasome inhibitor-based approaches to the treatment of relapsed/refractory multiple myeloma.
Abhishek Singla (2011)
[Thalidomide in treatment of connective diseases and vasculities].
Nicola Maruotti (2006)
Immunomodulatory drugs in multiple myeloma
Swati Andhavarapu (2013)
A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma.
Dharminder Chauhan (2010)
O TRATAMENTO E A SOBREVIDA NO MIELOMA MÚLTIPLO
Carolina Ashihara (2011)
A pharmacokinetic study evaluating the relationship between treatment efficacy and incidence of adverse events with thalidomide plasma concentrations in patients with refractory multiple myeloma.
Tomoko Kodama (2009)
MULTIPLE MYELOMA : FROM THE BENCH TO BEDSIDE Treatment options for relapsed and refractory multiple myeloma
Ajay K. Nooka (2015)
Antiangiogenic Therapy in Multiple Myeloma
Piero Tosi (2001)See more