对低甲基化药物和BCL-2抑制剂的耐药性机制

IF 2.2 4区 医学 Q3 HEMATOLOGY
Sudhamsh Reddy Desai , Samarpana Chakraborty , Aditi Shastri
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引用次数: 0

摘要

髓系恶性肿瘤,如骨髓增生异常综合征(MDS);急性髓性白血病(AML)是由于引起疾病的异常造血干细胞的扩张而出现和发展的克隆性疾病,传统的细胞毒性治疗无法消除。低甲基化药物(HMA)、阿扎胞苷(azacytidine)和地西他滨(decitabine)是治疗MDS的一线药物,与BCL-2抑制剂venetoclax联合被批准用于75岁以上患者的AML诱导,同时也在积极研究用于高风险MDS的药物。对这些药物的耐药性已成为髓系恶性肿瘤治疗的一个重大临床挑战。在这篇综述中,我们讨论了HMA和venetoclax耐药发展的分子机制。深入了解这些机制有助于识别潜在的耐药预测生物标志物,有助于开发联合疗法和预防耐药的策略,并推动癌症治疗领域的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mechanisms of resistance to hypomethylating agents and BCL-2 inhibitors

Myeloid malignancies such as myelodysplastic syndrome (MDS) & acute myeloid leukemia (AML) are clonal diseases that emerge and progress due to the expansion of disease-initiating aberrant hematopoietic stem cells, that are not eliminated by conventional cytotoxic therapies. Hypomethylating agents(HMA), azacytidine and decitabine are the first line agents for treatment of MDS and a combination with BCL-2 inhibitor, venetoclax, is approved for AML induction in patients above 75 years and is also actively being investigated for use in high risk MDS. Resistance to these drugs has become a significant clinical challenge in treatment of myeloid malignancies. In this review, we discuss molecular mechanisms underlying the development of resistance to HMA and venetoclax. Insights into these mechanisms can help identify potential biomarkers for resistance prediction, aid in the development of combination therapies and strategies to prevent resistance and advance the field of cancer therapeutics.

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来源期刊
CiteScore
4.20
自引率
0.00%
发文量
42
审稿时长
35 days
期刊介绍: Best Practice & Research Clinical Haematology publishes review articles integrating the results from the latest original research articles into practical, evidence-based review articles. These articles seek to address the key clinical issues of diagnosis, treatment and patient management. Each issue follows a problem-orientated approach which focuses on the key questions to be addressed, clearly defining what is known and not known, covering the spectrum of clinical and laboratory haematological practice and research. Although most reviews are invited, the Editor welcomes suggestions from potential authors.
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