通过GHRH拮抗剂MIA-602治疗AML的创新途径
A novel approach for the treatment of AML, through GHRH antagonism: MIA-602
影响因子:8.00000
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
摘要
急性髓系白血病（AML）是成人中最具侵袭性和高发的白血病类型。标准治疗主要依赖化疗，部分患者可能接受造血干细胞移植，但药物耐药是治疗中的常见难题。目前，除了姑息治疗外，针对难治性AML的临床手段有限。本综述旨在重新关注一种新型靶向激素治疗策略——生长激素释放激素（GHRH）拮抗剂，用于AML的治疗，因为它可能解决目前难以达成完全缓解的障碍。前期临床前证据显示，GHRH拮抗剂（GHRH-Ant）在体内外实验的人类AML细胞系中表现出显著的抗癌活性，并对药物耐药的白血病细胞系也具有明显的抑制作用。GHRH-Ant的作用机制包括与蒽环类药物不同的作用方式，联合使用时具有协同增强抗肿瘤效果。鉴于标准AML疗法的难题及耐药性的发展，MIA-602作为一种新颖的治疗途径，值得进一步深入研究。
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.