The Role of mTOR in B Cell Lymphoid Malignancies: Biologic and Therapeutic Aspects

Karatrasoglou, Eleni A.; Dimou, Maria; Piperidou, Alexia; Lakiotaki, Eleftheria; Korkolopoulou, Penelope; Vassilakopoulos, Theodoros P.

doi:10.3390/ijms241814110

IJMS

2023

DOI: 10.3390/ijms241814110

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The Role of mTOR in B Cell Lymphoid Malignancies: Biologic and Therapeutic Aspects

Eleni A. Karatrasoglou,

Maria Dimou,

Alexia Piperidou

et al.

Abstract: Non-Hodgkin lymphoma’s (NHL) incidence is rising over time, and B cell lymphomas comprise the majority of lymphomas. The phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue 1 (Akt)/mammalian target of the rapamycin (mTOR) signaling pathway plays a critical role in a variety of cellular processes, such as cell proliferation and survival. Its role in lymphomagenesis is confirmed in many different types of B cell lymphomas. This review is mainly focused on the PI3K/v-akt/mTOR pathway-re… Show more

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2024

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Cited by 3 publications

References 90 publications

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Marine sponge-derived alkaloid inhibits the PI3K/AKT/mTOR signaling pathway against diffuse large B-cell lymphoma

Liu,

Chang,

kou

et al. 2024

Med Oncol

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Marine sponge-derived alkaloid inhibits the PI3K/AKT/mTOR signaling pathway against diffuse large B-cell lymphoma

Liu,

Chang,

kou

et al. 2024

Med Oncol

View full text Add to dashboard Cite

Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review

Masnikosa,

Cvetković,

Pirić

2024

IJMS

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Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over the years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline the DLBCL tumor biology behind the actual and potential drug targets and address the challenges and drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody–drug conjugates, chimeric antigen receptors, bispecific antibodies and T-cell engagers, and immune checkpoint inhibitors. Candidate drugs explored in ongoing clinical trials are coupled with diverse toxicity issues and refractoriness to drugs. According to the literature on DLBCL, the promise for new therapeutic targets lies in epigenetic alterations, B-cell receptor and NF-κB pathways. Herein, we present putative targets hiding in lipid pathways, ferroptosis, and the gut microbiome that could be used in addition to immuno-chemotherapy to improve the general health status of DLBCL patients, thus increasing the chance of being cured. It may be time to devote more effort to exploring DLBCL metabolism to discover novel druggable targets. We also performed a bibliometric and knowledge-map analysis of the literature on DLBCL published from 2014–2023.

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Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements on Life Span in y w Male Drosophila melanogaster

Bearden,

Stewart,

Casher

et al. 2024

IJMS

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Various dietary supplements have been shown to extend the life span of Drosophila melanogaster, including several that promote autophagy, such as rapamycin and spermidine. The goal of the study presented here was to test numerous additional potential anti-aging supplements, primarily inhibitors of the target of rapamycin (TOR) and/or phosphatidylinositol 3-kinase (PI3K). Using a single, comparatively long-lived y w test strain, screening was performed in male flies supplemented either throughout adulthood or, in a few cases, beginning in middle or late adult life, with concentrations spanning 4–6 orders of magnitude in most cases. Supplementation with PP242 and deferiprone, an iron chelator, beginning in late adult life had no positive effect on life span. Lifelong supplementation with Ku-0063794, LY294002, PX-866-17OH, Torin2 and WYE-28 had no effect at any dose. Rapamycin, spermidine and wortmannin all had significant life-shortening effects at the highest doses tested. AZD8055, PI-103 hydrochloride and WYE-132 yielded slight beneficial effects at 1–2 doses, but only 100 nM AZD8055 was confirmed to have a minor (1.3%) effect in a replicate experiment, which was encompassed by other control groups within the same study. These compounds had no effect on fly fecundity (egg laying) or fertility (development of progeny to adulthood), but equivalent high doses of rapamycin abolished fertility. The solvent DMSO had no significant effect on life span at the concentrations used to solubilize most compounds in the fly medium, but it drastically curtailed both survival and fertility at higher concentrations. 2-Hydroxypropyl-β-cyclodextrin also failed to extend the life span when provided throughout adulthood or beginning in mid-adult life. Collectively, the results suggest that inhibition of the TOR/PI3K pathway and autophagy through dietary intervention is not a straightforward anti-aging strategy in Drosophila and that further extension of life is difficult in comparatively long-lived flies.

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The Role of mTOR in B Cell Lymphoid Malignancies: Biologic and Therapeutic Aspects

Cited by 3 publications

References 90 publications

Marine sponge-derived alkaloid inhibits the PI3K/AKT/mTOR signaling pathway against diffuse large B-cell lymphoma

Marine sponge-derived alkaloid inhibits the PI3K/AKT/mTOR signaling pathway against diffuse large B-cell lymphoma

Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review

Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements on Life Span in y w Male Drosophila melanogaster

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