Unraveling the complexity of drug resistance mechanisms to SINE, T cell-engaging therapies and CELMoDs in multiple myeloma: a comprehensive review.

IF 4.6 Q1 ONCOLOGY 癌症耐药(英文) Pub Date : 2024-06-26 eCollection Date: 2024-01-01 DOI:10.20517/cdr.2024.39
Jacqueline Schütt, Kerstin Brinkert, Andrzej Plis, Tino Schenk, Annamaria Brioli
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Abstract

Despite significant advances in the understanding of multiple myeloma (MM) biology and the development of novel treatment strategies in the last two decades, MM is still an incurable disease. Novel drugs with alternative mechanisms of action, such as selective inhibitors of nuclear export (SINE), modulators of the ubiquitin pathway [cereblon E3 ligase modulatory drugs (CELMoDs)], and T cell redirecting (TCR) therapy, have led to significant improvement in patient outcomes. However, resistance still emerges, posing a major problem for the treatment of myeloma patients. This review summarizes current data on treatment with SINE, TCR therapy, and CELMoDs and explores their mechanism of resistance. Understanding these resistance mechanisms is critical for developing strategies to overcome treatment failure and improve therapeutic outcomes.

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揭示多发性骨髓瘤中SINE、T细胞激活疗法和CELMoDs耐药机制的复杂性:综述。
尽管在过去二十年里,人们对多发性骨髓瘤(MM)生物学的认识和新型治疗策略的开发取得了重大进展,但MM仍然是一种无法治愈的疾病。具有替代作用机制的新型药物,如核输出选择性抑制剂(SINE)、泛素通路调节剂[脑龙E3连接酶调节药物(CELMoDs)]和T细胞重定向(TCR)疗法,已使患者的预后得到显著改善。然而,耐药性依然存在,给骨髓瘤患者的治疗带来了重大问题。本综述总结了目前有关SINE、TCR疗法和CELMoDs治疗的数据,并探讨了它们的耐药机制。了解这些耐药机制对于制定克服治疗失败和改善治疗效果的策略至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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