ReviewDrug design, development and therapy2025
Current Knowledge of the Integrated Stress Response in the Development and Management of Acute Myeloid Leukemia: A Novel Target with Encouraging Progress.
Review in Drug design, development and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Review
- Redefining success in assisted reproductive technologies: the Embryo-Maternal-Offspring Continuum Framework.Journal of assisted reproduction and genetics · 2026Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary or acquired resistance to standard chemotherapy and novel targeted therapies remains a common cause of relapsed/refractory acute myeloid leukemia (AML). The five-year overall survival rate for AML patients remains poor. Exploring novel therapeutic pathways may offer effective strategies to address this challenge. The Integrated Stress Response (ISR) is a signaling pathway that maintains cellular homeostasis by reducing global protein synthesis in response to external and internal stressors. Recent studies have demonstrated that ISR exerts a dual role in AML. Moderate activation of ISR supports hematopoietic and leukemia stem cell maintenance and promotes AML progression, whereas hyperactivation of ISR induces apoptosis and reduces myeloid cell leukemia-1 (MCL-1) expression. MCL-1 overexpression contributes to venetoclax resistance. However, MCL-1 inhibitors have shown disappointing cardiac toxicity in clinical studies. Hyperactivation of the ISR can indirectly suppress MCL-1 and help reverse venetoclax (ABT-199) resistance, as reported in previous studies. Our previous study also indicates that ISR activation can reverse venetoclax resistance in AML cells. These findings support the ISR as a novel therapeutic target in AML. However, the mechanisms by which ISR influences stemness and resistance are not yet fully understood. This review integrates current mechanistic insights and preclinical evidence to highlight the ISR as both a key driver of leukemogenesis and a promising target for overcoming drug resistance in AML. We searched the literature up to October 2025 in PubMed, Google Scholar, and ClinicalTrials.gov using terms related to AML, ISR signaling, venetoclax, and ISR kinases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.