通过GHRH拮抗剂MIA-602创新性治疗AML的方法
A novel approach for the treatment of AML, through GHRH antagonism: MIA-602
DOI 原文链接
用sci-hub下载
如无法下载，请从 Sci-Hub 选择可用站点尝试。
影响因子:8
分区:医学2区 / 内分泌学与代谢2区
发表日期:2025 Jun
作者:
Joel Costoya, Simonetta I Gaumond, Ravinder S Chale, Andrew V Schally, Joaquin J Jimenez
DOI:
10.1007/s11154-024-09917-6
摘要
急性髓系白血病（AML）是成人中最具侵袭性和患病率最高的白血病类型。其金标准治疗主要依赖化疗，在某些情况下还包括造血干细胞移植。药物耐药是治疗中常见的并发症，目前除姑息治疗外，针对难治性AML的临床措施有限。本文旨在重新激发对一种新型靶向激素治疗的兴趣，即利用生长激素释放激素（GHRH）拮抗剂治疗AML，因为它可能为解决当前达到完全缓解的障碍提供潜在途径。根据前临床证据，GHRH拮抗剂（GHRH-Ant）在体外和体内的实验性人类AML细胞系中表现出显著的抗癌活性，并在耐药白血病细胞系的药物耐药模型中也显示出显著的抗肿瘤作用。GHRH-Ant的作用机制与蒽环类药物正交，当联合使用时可协同增强抗肿瘤效果。考虑到标准AML治疗的难题及药物耐药问题，MIA-602代表了一种值得深入研究的创新策略。
Abstract
Acute myeloid leukemia (AML) is the most aggressive and prevalent form of leukemia in adults. The gold-standard intervention revolves around the use of chemotherapy, and in some cases hematopoietic stem cell transplantation. Drug resistance is a frequent complication resulting from treatment, as it stands there are limited clinical measures available for refractory AML besides palliative care. The goal of this review is to renew interest in a novel targeted hormone therapy in the treatment of AML utilizing growth hormone-releasing hormone (GHRH) antagonism, given it may provide a potential solution for current barriers to achieving complete remission post-therapy. Recapitulating pre-clinical evidence, GHRH antagonists (GHRH-Ant) have significant anti-cancer activity across experimental human AML cell lines in vitro and in vivo and demonstrate significant inhibition of cancer in drug resistant analogs of leukemic cell lines as well. GHRH-Ant act in manners that are orthogonal to anthracyclines and when administered in combination synergize to produce a more potent anti-neoplastic effect. Considering the adversities associated with standard AML therapies and the developing issue of drug resistance, MIA-602 represents a novel approach worth further investigation.