GHRH antagonist MIA-602 reduces leukemic growth in acute myeloid leukemia models, targeting drug resistance

Acute myeloid leukemia (AML) is a severe hematological malignancy characterized by the uncontrolled expansion of immature myeloid progenitors, leading to poor 5-year survival rates. While targeted therapies like FLT3 inhibitors and IDH inhibitors have improved outcomes for specific genetic lesions, therapeutic resistance remains a critical barrier to durable remission. Growth hormone-releasing hormone (GHRH) and its receptor (GHRH-R) are implicated in various cancers, with GHRH antagonists demonstrating anti-neoplastic activity. GHRH-R has been identified in several experimental AML models, including drug-resistant sublines, suggesting it as a potential therapeutic target.

Researchers investigated the GHRH antagonist MIA-602 as a potential therapeutic agent in acute myeloid leukemia (AML) models. The study encompassed both in vitro experiments using leukemic cell lines and in vivo studies involving xenografted tumors in nude mice. The primary objective was to evaluate the impact of MIA-602 on leukemic cell growth and proliferation. Treatment with MIA-602 was administered, and its effects were monitored over time and across different doses to determine its efficacy against AML, particularly in the context of drug resistance.

Treatment with the GHRH antagonist MIA-602 resulted in a significant time- and dose-dependent reduction in leukemic growth. This inhibitory effect was consistently observed across both in vitro cell culture models and in vivo xenograft models of acute myeloid leukemia. The presence of GHRH receptor (GHRH-R) was confirmed in several experimental AML models, notably including drug-resistant sublines, highlighting its potential as a therapeutic target in refractory disease. The abstract notes that FLT3 inhibitor resistance is often linked to the activation of PI3K/AKT and ERK/MAPK pathways, as well as inflammatory and apoptotic escape mechanisms. While specific quantitative data (e.g., percentages of reduction, p-values) were not provided in the abstract, the qualitative finding of significant growth inhibition was consistent. The authors hypothesize that GHRH-R antagonism could modulate these resistance-associated signaling networks.

MIA-602 treatment led to a significant time- and dose-dependent reduction in leukemic growth in both in vitro and in vivo models of acute myeloid leukemia.