肿瘤细胞治疗研究
英文原题：Acute myeloid leukemia resistant to venetoclax-based therapy: What does the future hold?
维奈克拉是一种高选择性 B 细胞淋巴瘤-2（BCL-2）抑制剂，与 DNA 低甲基化药物或低剂量阿糖胞苷联合使用，可使急性髓系白血病（AML）患者获得较高的初始缓解率。
维奈克拉是一种高选择性B细胞淋巴瘤2（BCL-2）抑制剂，与DNA低甲基化药物或低剂量阿糖胞苷联合使用，可使急性髓系白血病（AML）患者获得较高的初始应答率。然而，多数患者最终会复发。维奈克拉方案耐药机制包括TP53基因突变或p53蛋白失活、FLT3和RAS等激活性激酶突变，以及其他BCL-2家族凋亡相关蛋白上调。目前的临床试验正探索多种策略，例如在双联或三联方案中加入p53激活剂、抗CD47抗体，或靶向维奈克拉耐药相关基因和蛋白的新型药物。未来研究还应着重识别维奈克拉方案疗效的预测性生物标志物，并结合免疫治疗策略，包括免疫检查点抑制剂、双特异性抗体、抗体药物偶联物和CAR T细胞疗法，以改善AML患者结局。
Venetoclax is a highly selective B-cell lymphoma-2 (BCL-2) inhibitor, which, combined with a DNA hypomethylating agent or low dose cytarabine, results in high rates of initial responses in patients with acute myeloid leukemia (AML). However, the disease relapses in most patients. Mechanisms of resistance to venetoclax-based therapy include TP53 gene mutations or inactivation of p53 protein, activating kinase mutations such as FLT3 and RAS, and upregulation of other BCL-2 family apoptotic proteins. Current clinical trials are exploring strategies such as doublet or triplet regimens incorporating a p53 activator, an anti-CD47 antibody, or other novel agents that target genes and proteins responsible for resistance to venetoclax. Further studies should focus on identifying predictive biomarkers of response to venetoclax-based therapy and incorporating immunotherapeutic approaches such as checkpoint inhibitors, bispecific antibodies, antibody-drug conjugates, and CAR T-cell therapy to improve outcomes for patients with AML.
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