Costoya Joel, Gaumond Simonetta I, Chale Ravinder S, Schally Andrew V, Jimenez Joaquin J
Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA.
Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA.
Rev Endocr Metab Disord. 2025 Jun;26(3):483-491. doi: 10.1007/s11154-024-09917-6. Epub 2024 Oct 17.
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.
急性髓系白血病(AML)是成人中最具侵袭性和最常见的白血病形式。金标准干预措施主要围绕化疗的使用,在某些情况下还包括造血干细胞移植。耐药性是治疗中常见的并发症,目前除了姑息治疗外,针对难治性AML的临床措施有限。本综述的目的是重新激发人们对一种新型靶向激素疗法治疗AML的兴趣,该疗法利用生长激素释放激素(GHRH)拮抗作用,因为它可能为当前治疗后实现完全缓解的障碍提供潜在解决方案。总结临床前证据,GHRH拮抗剂(GHRH-Ant)在体外和体内的实验性人类AML细胞系中均具有显著的抗癌活性,并且在白血病细胞系的耐药类似物中也显示出对癌症的显著抑制作用。GHRH-Ant的作用方式与蒽环类药物不同,联合使用时会协同产生更强的抗肿瘤作用。考虑到标准AML疗法的不良反应和耐药性这一不断发展的问题,MIA-602代表了一种值得进一步研究的新方法。