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Absence of mutations in cereblon (CRBN) and DNA damage-binding protein 1 (DDB1) genes and significance for IMiD therapy.
Thakurta A, Gandhi AK, Waldman MF, Bjorklund C, Ning Y, Mendy D, Schafer P, Lopez-Girona A, Lentzsch S, Schey SA, Calle Y, Chelliah R, Orlowski RZ, Madan A, Avet-Loiseau H, Chopra R. Thakurta A, et al. Among authors: schafer p. Leukemia. 2014 May;28(5):1129-31. doi: 10.1038/leu.2013.315. Epub 2013 Oct 29. Leukemia. 2014. PMID: 24166296 Free PMC article. No abstract available.
Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.
Lopez-Girona A, Mendy D, Ito T, Miller K, Gandhi AK, Kang J, Karasawa S, Carmel G, Jackson P, Abbasian M, Mahmoudi A, Cathers B, Rychak E, Gaidarova S, Chen R, Schafer PH, Handa H, Daniel TO, Evans JF, Chopra R. Lopez-Girona A, et al. Among authors: schafer ph. Leukemia. 2012 Nov;26(11):2326-35. doi: 10.1038/leu.2012.119. Epub 2012 May 3. Leukemia. 2012. PMID: 22552008 Free PMC article.
Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity.
Gandhi AK, Mendy D, Waldman M, Chen G, Rychak E, Miller K, Gaidarova S, Ren Y, Wang M, Breider M, Carmel G, Mahmoudi A, Jackson P, Abbasian M, Cathers BE, Schafer PH, Daniel TO, Lopez-Girona A, Thakurta A, Chopra R. Gandhi AK, et al. Among authors: schafer ph. Br J Haematol. 2014 Jan;164(2):233-44. doi: 10.1111/bjh.12622. Epub 2013 Oct 28. Br J Haematol. 2014. PMID: 24206017 Free PMC article.
Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.).
Gandhi AK, Kang J, Havens CG, Conklin T, Ning Y, Wu L, Ito T, Ando H, Waldman MF, Thakurta A, Klippel A, Handa H, Daniel TO, Schafer PH, Chopra R. Gandhi AK, et al. Br J Haematol. 2014 Mar;164(6):811-21. doi: 10.1111/bjh.12708. Epub 2013 Dec 13. Br J Haematol. 2014. PMID: 24328678 Free PMC article.
CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL.
Hagner PR, Man HW, Fontanillo C, Wang M, Couto S, Breider M, Bjorklund C, Havens CG, Lu G, Rychak E, Raymon H, Narla RK, Barnes L, Khambatta G, Chiu H, Kosek J, Kang J, Amantangelo MD, Waldman M, Lopez-Girona A, Cai T, Pourdehnad M, Trotter M, Daniel TO, Schafer PH, Klippel A, Thakurta A, Chopra R, Gandhi AK. Hagner PR, et al. Blood. 2015 Aug 6;126(6):779-89. doi: 10.1182/blood-2015-02-628669. Epub 2015 May 22. Blood. 2015. PMID: 26002965 Free PMC article. Clinical Trial.
Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomide-induced immunomodulation of T and NK cell function.
Gandhi AK, Kang J, Capone L, Parton A, Wu L, Zhang LH, Mendy D, Lopez-Girona A, Tran T, Sapinoso L, Fang W, Xu S, Hampton G, Bartlett JB, Schafer P. Gandhi AK, et al. Among authors: schafer p. Curr Cancer Drug Targets. 2010 Mar;10(2):155-67. doi: 10.2174/156800910791054239. Curr Cancer Drug Targets. 2010. PMID: 20088798
Lenalidomide downregulates the cell survival factor, interferon regulatory factor-4, providing a potential mechanistic link for predicting response.
Lopez-Girona A, Heintel D, Zhang LH, Mendy D, Gaidarova S, Brady H, Bartlett JB, Schafer PH, Schreder M, Bolomsky A, Hilgarth B, Zojer N, Gisslinger H, Ludwig H, Daniel T, Jäger U, Chopra R. Lopez-Girona A, et al. Br J Haematol. 2011 Aug;154(3):325-36. doi: 10.1111/j.1365-2141.2011.08689.x. Epub 2011 Jun 24. Br J Haematol. 2011. PMID: 21707574 Free article.
503 results