Biological Activity of Lenalidomide and Its Underlying Therapeutic Effects in Multiple Myeloma

Overview

Journal Adv Hematol

Publisher Wiley

Specialty Hematology

Date 2012 Aug 25

PMID 22919394

Citations 25

Authors

Roberta Martiniani

Valentina Di Loreto

Chiara Di Sano

Alessandra Lombardo

Anna Marina Liberati

Affiliations

Soon will be listed here.

Abstract

Lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide. It belongs to the second generation of immunomodulatory drugs (IMiDs) and possesses pleiotropic properties. Even if lenalidomide has been shown to be active in the treatment of several hematologic malignancies, this review article is mostly focalized on its mode of action in multiple myeloma. The present paper is about the direct and indirect antitumor effects of lenalidomide on malignant plasmacells, bone marrow microenvironment, bone resorption and host's immune response. The molecular mechanisms and targets of lenalidomide remain largely unknown, but recent evidence shows cereblon (CRBN) as a possible mediator of its therapeutical effects.

Citing Articles

Cancer drugs with high repositioning potential for Alzheimer's disease.

Majeed J, Sabbagh M, Kang M, Lawrence J, Pruitt K, Bacus S Expert Opin Emerg Drugs. 2023; 28(4):311-332.

PMID: 38100555 PMC: 10877737. DOI: 10.1080/14728214.2023.2296079.

Lenalidomide in Multiple Myeloma: Review of Resistance Mechanisms, Current Treatment Strategies and Future Perspectives.

Kulig P, Milczarek S, Bakinowska E, Szalewska L, Baumert B, Machalinski B Cancers (Basel). 2023; 15(3).

PMID: 36765919 PMC: 9913106. DOI: 10.3390/cancers15030963.

The emerging therapeutic landscape of relapsed/refractory multiple myeloma.

Tanenbaum B, Miett T, Patel S Ann Hematol. 2022; 102(1):1-11.

PMID: 36462062 PMC: 10888499. DOI: 10.1007/s00277-022-05058-5.

Lenalidomide potentially reduced the level of cell- associated HIV RNA and improved persistent inflammation in patients with HIV-associated cryptococcal meningitis a pilot study.

Liu X, Zhu X, Peng X, Tao R, Wan Z, Hui J Front Cell Infect Microbiol. 2022; 12:954814.

PMID: 35967862 PMC: 9369255. DOI: 10.3389/fcimb.2022.954814.

A quantitative view of strategies to engineer cell-selective ligand binding.

Tan Z, Orcutt-Jahns B, Meyer A Integr Biol (Camb). 2021; 13(11):269-282.

PMID: 34931243 PMC: 8730367. DOI: 10.1093/intbio/zyab019.

References

Richardson P, Weller E, Lonial S, Jakubowiak A, Jagannath S, Raje N . Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010; 116(5):679-86. PMC: 3324254. DOI: 10.1182/blood-2010-02-268862. View

Gertz M, Comenzo R, Falk R, Fermand J, Hazenberg B, Hawkins P . Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol. 2005; 79(4):319-28. DOI: 10.1002/ajh.20381. View

Kotla V, Goel S, Nischal S, Heuck C, Vivek K, Das B . Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009; 2:36. PMC: 2736171. DOI: 10.1186/1756-8722-2-36. View

Hideshima T, Chauhan D, Schlossman R, Richardson P, Anderson K . The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene. 2001; 20(33):4519-27. DOI: 10.1038/sj.onc.1204623. View

Brown R, Pope B, Murray A, Esdale W, Sze D, Gibson J . Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta1 and interleukin-10. Blood. 2001; 98(10):2992-8. DOI: 10.1182/blood.v98.10.2992. View

Heintel D, Rocci A, Ludwig H, Bolomsky A, Caltagirone S, Schreder M . High expression of cereblon (CRBN) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone. Br J Haematol. 2013; 161(5):695-700. DOI: 10.1111/bjh.12338. View

Jarahian M, Watzl C, Issa Y, Altevogt P, Momburg F . Blockade of natural killer cell-mediated lysis by NCAM140 expressed on tumor cells. Int J Cancer. 2007; 120(12):2625-34. DOI: 10.1002/ijc.22579. View

List A, Kurtin S, Roe D, Buresh A, Mahadevan D, Fuchs D . Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005; 352(6):549-57. DOI: 10.1056/NEJMoa041668. View

Cang Y, Zhang J, Nicholas S, Kim A, Zhou P, Goff S . DDB1 is essential for genomic stability in developing epidermis. Proc Natl Acad Sci U S A. 2007; 104(8):2733-7. PMC: 1797626. DOI: 10.1073/pnas.0611311104. View

10.

Puthier D, Bataille R, Amiot M . IL-6 up-regulates mcl-1 in human myeloma cells through JAK / STAT rather than ras / MAP kinase pathway. Eur J Immunol. 1999; 29(12):3945-50. DOI: 10.1002/(SICI)1521-4141(199912)29:12<3945::AID-IMMU3945>3.0.CO;2-O. View

11.

Tariman J . Lenalidomide: a new agent for patients with relapsed or refractory multiple myeloma. Clin J Oncol Nurs. 2007; 11(4):569-74. DOI: 10.1188/07.CJON.569-574. View

12.

Chauhan D, Hideshima T, Anderson K . Apoptotic signaling in multiple myeloma: therapeutic implications. Int J Hematol. 2003; 78(2):114-20. DOI: 10.1007/BF02983378. View

13.

Dimopoulos M, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer E . Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009; 23(11):2147-52. DOI: 10.1038/leu.2009.147. View

14.

Hideshima T, Bergsagel P, Kuehl W, Anderson K . Advances in biology of multiple myeloma: clinical applications. Blood. 2004; 104(3):607-18. DOI: 10.1182/blood-2004-01-0037. View

15.

Verhelle D, Corral L, Wong K, Mueller J, Moutouh-de Parseval L, Jensen-Pergakes K . Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res. 2007; 67(2):746-55. DOI: 10.1158/0008-5472.CAN-06-2317. View

16.

Chu Z, McKinsey T, Liu L, Gentry J, Malim M, Ballard D . Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kappaB control. Proc Natl Acad Sci U S A. 1997; 94(19):10057-62. PMC: 23303. DOI: 10.1073/pnas.94.19.10057. View

17.

Terpos E, Dimopoulos M, Sezer O . The effect of novel anti-myeloma agents on bone metabolism of patients with multiple myeloma. Leukemia. 2007; 21(9):1875-84. DOI: 10.1038/sj.leu.2404843. View

18.

Bergsagel P, Kuehl W . Critical roles for immunoglobulin translocations and cyclin D dysregulation in multiple myeloma. Immunol Rev. 2003; 194:96-104. DOI: 10.1034/j.1600-065x.2003.00052.x. View

19.

Dai Y, Dent P, Grant S . Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotes mitochondrial dysfunction and apoptosis induced by 7-hydroxystaurosporine and mitogen-activated protein kinase kinase inhibitors in human leukemia cells that ectopically.... Mol Pharmacol. 2003; 64(6):1402-9. DOI: 10.1124/mol.64.6.1402. View

20.

LeBlanc R, Hideshima T, Catley L, Shringarpure R, Burger R, Mitsiades N . Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood. 2003; 103(5):1787-90. DOI: 10.1182/blood-2003-02-0361. View