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Epigenetic Therapies for Acute Myeloid Leukemia and Their Immune-Related Effects.

Over the past decades, our molecular understanding of acute myeloid leukemia (AML) pathogenesis dramatically increased, thanks also to the advent of next-generation sequencing (NGS) technologies. Many of these findings, however, have not yet translated into new prognostic markers or rationales for treatments. We now know that AML is a highly heterogeneous disease characterized by a very low mutational burden. Interestingly, the few mutations identified mainly reside in epigenetic regulators, which shape and define leukemic cell identity. In the light of these discoveries and given the increasi

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… A recent study showed that the LSD1 inhibitor tranylcypromine (TCP) induced the expression of myeloid differentiation genes in AML cells and that combination of TCP with ATRA exerted a potent anti-leukemic effect ( Schenk et al., 2012 ). …

One step further in targeting acute leukemia by combining antibody-based immunotherapies and small molecule inhibitors.

BackgroundAcute leukemia is a bone marrow-related disease characterized by fast progression and the production of immature blood cells rather than normal ones that are classified as either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Chemotherapy as a conventional treatment has many side effects, thus new medications that target intracellular molecules and cell surface markers on leukemic cells have been developed in the last decades.Main bodyThis review focuses on antibody-based targeted treatments, which so far, have been shown to improve the treatment outcomes, includ

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… Tranylcypromine (TCP) emerged as the first compound that was capable of inhibiting LSD1 catalytic activity [ 125 ]. …

Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.

Epigenetics shapes all aspects of cancer occurrence and progression. Among them, chromatin methylation is a particularly important regulator of oncogenic processes. The dynamic shifts in methylation can influence the development or death of tumor cells. In the therapeutic context, effectively targeting and modulating DNA, RNA, and histone methylation brings promise for the early detection, prognostic assessment, and treatment of cancer. In particular, novel methylation inhibitors or modulators powerfully kill tumor cells or improve existing therapeutic strategies through different signaling pa

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… Bisantrene/Fludarabine/Clofarabine Acute myeloid leukemia II, 2021 NCT04989335 LSD1 inhibitor/Chemotherapy Seclidemstat/Cyclophosphamide/Topotecan Ewing sarcomas I, 2018 NCT03600649 LSD1 inhibitor/Chemotherapy Bomedemstat/Venetoclax Acute myeloid leukemia I, 2022 NCT05597306 LSD1 inhibitor/Chemotherapy Tranylcypromine … Clofarabine | Acute myeloid leukemia | II, 2021 | NCT04989335 LSD1 inhibitor/Chemotherapy | Seclidemstat/Cyclophosphamide/Topotecan | Ewing sarcomas | I, 2018 | NCT03600649 LSD1 inhibitor/Chemotherapy | Bomedemstat/Venetoclax | Acute myeloid leukemia | I, 2022 | NCT05597306 LSD1 inhibitor/Chemotherapy | Tranylcypromine …

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

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… Table 1 Summary of completed clinical trials of nuclear receptor-targeted drugs Target NCT Number Results Conditions Agents Phases Retinoic acid receptor-α (RARα) NCT02273102 COMPLETED (No Results Posted) Acute Myelogenous Leukemia; Myelodysplastic Syndromes; Leukemia Tranylcypromine; Tretinoin PHASE1 …

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic

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… /R | NCT03572387 | Icahn School of Medicine at Mount Sinai Anastrozole | Breast Neoplasm | 2/R | NCT04113863 | Mario Negri Inst for Pharm Research - | Leukemia | R | NCT01064557 | Gruppo Italiano Malattie VEGFR inhibitor | Adenoid Cystic Carcinoma | 2/R | NCT04433169 | Shanghai Jiao Tong University Tranylcypromine …

The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.

Cancer development and progression are increasingly understood to arise from dynamic interactions between genetic alterations and environmentally driven epigenetic regulation, with dietary exposures representing one of the most biologically influential and modifiable factors. Given the expanding evidence linking nutrition to epigenomic remodeling, a comprehensive synthesis of how specific dietary components influence cancer-relevant epigenetic mechanisms is needed to clarify their preventive and therapeutic relevance. This review brings together mechanistic, epidemiologic, and translational fi

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… Notably, MAO inhibitors such as tranylcypromine and phenelzine have been found to inhibit LSD1 activity, suggesting a pharmacological intersection with potential implications for neurological disease management [ 110 ]. …

Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.

Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lympho