Exploiting Metabolic Vulnerabilities in Acute Myeloid Leukemia: Rationale and Evidence for Combining Metabolic Modulators with Conventional Chemotherapy
Abstract
Acute myeloid leukemia (AML) represents a heterogeneous group of hematological malignancies characterized by uncontrolled proliferation of myeloid progenitors and accumulation of immature blasts in the bone marrow. Metabolic reprogramming is now recognized as a core hallmark of AML, generating dependencies that distinguish leukemic cells from normal hematopoietic stem and progenitor cells and that can be exploited therapeutically. In this review we follow a single connected line of argument: we first place metabolic rewiring within the broader hallmarks of cancer, then describe the principal metabolic programs altered in AML and the specific features that distinguish AML from other malignancies. We next examine the inhibitors and drugs that target each of these pathways, linking every drug class to its mechanism of synergy with chemotherapy, the preclinical and clinical evidence available, and its association with outcome in AML. We then consider multi-target (combination) therapy as a distinct opportunity, and finally the principal challenges that remainsafety and tolerability, the metabolic heterogeneity and plasticity of AML, and the design of biomarker-guided trials. Multiple classes of metabolic drugs are discussed, including glycolysis inhibitors, oxidative phosphorylation inhibitors, glutamine metabolism antagonists, fatty acid oxidation modulators, and redox-active compounds. Despite significant challenges, targeting cellular metabolism represents a promising…
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.