Author:
Wang Shichao,Li Zhiyue,Gao Shaobing
Abstract
AbstractImmunomodulatory drugs (IMiDs) include thalidomide, lenalidomide, and pomalidomide, which have shown significant efficacy in the treatment of multiple myeloma (MM), myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) and other hematological malignancies. IMiDs hijack the CRL4CRBN ubiquitin ligase to target cellular proteins for ubiquitination and degradation, which is responsible for their clinical activity in MM and MDS with del(5q). However, intrinsic and acquired resistance frequently limit the efficacy of IMiDs. Recently, many efforts have been made to explore key regulators of IMiD sensitivity, resulting in great advances in the understanding of the regulatory networks related to this class of drugs. In this review, we describe the mechanism of IMiDs in cancer treatment and summarize the key regulators of IMiD sensitivity. Furthermore, we introduce genome-wide CRISPR-Cas9 screenings, through which the regulatory networks of IMiD sensitivity could be identified.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Biochemistry (medical),Clinical Biochemistry,Molecular Medicine
Reference127 articles.
1. Sampaio EP. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med. 1991;173(3):699–703.
2. Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, Patterson RT, Stirling DI, Kaplan G. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol. 1999;163(1):380–6.
3. Haslett PA, Klausner JD, Makonkawkeyoon S, Moreira A, Metatratip P, Boyle B, Kunachiwa W, Maneekarn N, Vongchan P, Corral LG, et al. Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients. AIDS Res Hum Retroviruses. 1999;15(13):1169–79.
4. Davies FE, Raje N, Hideshima T, Lentzsch S, Young G, Tai YT, Lin B, Podar K, Gupta D, Chauhan D, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood. 2001;98(1):210–6.
5. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341(21):1565–71.
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