Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics

Tabnak, Peyman; Hasanzade Bashkandi, Aysa; Ebrahimnezhad, Mohammad; Soleimani, Mahdieh

doi:10.1186/s12935-023-03090-7

Cited by 7 publications

(3 citation statements)

References 225 publications

(217 reference statements)

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“…Many studies pointed out the FOXM1 role in regulating DNA damage response [45, 46, 47]. In pediatric glioma, it has been shown that inhibition of PI3K reduces the DNA repair functions by a pathway involving FOXM1 .…”

Section: Resultsmentioning

confidence: 99%

Exploring glioma heterogeneity through omics networks: from gene network discovery to causal insights and patient stratification

Kastendiek,

Coletti,

Gross

et al. 2024

Preprint

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Gliomas are primary malignant brain tumors with a typically poor prognosis, exhibiting significant heterogeneity across different cancer types. Each glioma type possesses distinct molecular characteristics determining patient prognosis and therapeutic options. This study aims to explore the molecular complexity of gliomas at the transcriptome level, employing a comprehensive approach grounded in network discovery. The graphical lasso method was used to estimate a gene co-expression network for each glioma type from a transcriptomics dataset. Causality was subsequently inferred from correlation networks by estimating the Jacobian matrix. The networks were then analyzed for gene importance using centrality measures and modularity detection, leading to the selection of genes that might play an important role in the disease. Spectral clustering based on patient similarity networks was applied to stratify patients into groups with similar molecular characteristics and to assess whether the resulting clusters align with the diagnosed glioma type. The results presented highlight the ability of the proposed methodology to uncover relevant genes associated with glioma intertumoral heterogeneity. Further investigation might encompass biological validation of the putative biomarkers disclosed.

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Section: Resultsmentioning

confidence: 99%

Exploring glioma heterogeneity through omics networks: from gene network discovery to causal insights and patient stratification

Kastendiek,

Coletti,

Gross

et al. 2024

Preprint

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“…This vaccine is currently being evaluated in a multicenter phase Ib/IIa clinical trial (EOGBM1-18, NCT04116658) in patients with recurrent glioblastoma. The selection of these primary targets (IL-13RA2, BIRC5, and FOXM1) in GBM approach is supported by prior scientific or clinical data validating these tumors antigens as well express TAA in tumor cells of GBM patients (55)(56)(57). Initial immunomonitoring data obtained from blood samples of three patients included in the first cohort demonstrated that this approach is unique among other peptide-based therapies in its ability to generate robust CD8+ T cell responses.…”

Section: Discussionmentioning

confidence: 97%

A Mimicry-Based Strategy Between Human and Commensal Antigens for the Development of a New Family of Immune Therapies for Cancer

Talpin,

Maia,

Carpier

et al. 2024

Preprint

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Peptide vaccines have emerged as a promising strategy for cancer immunotherapy, yet often lack of strong, specific and sustained immune responses against tumor antigens. To achieve a robust immune response, the effective selection of tumour antigens is crucial. While neoantigens trigger potent immune responses, their use suffers from patient specificity and their rarity in low-mutational tumors. Alternatively, the immunogenic potential of tumor-associated antigens (TAAs) is limited by central immune tolerance. Molecular mimicry and T cell cross-reactivity is a proposed mechanism to trigger a robust T cell-mediated antitumor response. Although molecular mimicry between pathogens and tumor antigens has been described, the potential benefits of exploiting this molecular mimicry with commensal bacterial antigens in antitumor immunity have not been thoroughly investigated despite strong evidence that the composition of the human microbiota significantly influences immune competency. Our new approach called OncoMimics™, which uses molecular mimicry between commensal bacterial and tumoral antigens to induce cross-reactive cytotoxic T cells against tumor cells. In preclinical studies, vaccination with OncoMimic™ peptides (OMPs) led to the expansion of CD8+T cells reacting against homologous tumor-associated antigen peptides and elicits cytotoxic activity against tumor cells. OMPs are efficiently recognized by a prevalent T cell population within the peripheral blood mononuclear cells of healthy individuals. An ongoing clinical trial (NCT04116658) using OncoMimics™ in patients with glioblastoma demonstrates early, durable, and cross-reactive tumor antigen CD8+T cell responses with pronounced memory persistence. By overcoming the current vaccine limitations, OncoMimics™ constitutes a promising strategy for enhancing cancer immunity and improving patient outcomes.Statement of SignificanceThis study introduces OncoMimics™, a peptide-based immunotherapy leveraging molecular mimicry to induce robust, cross-reactive T cell responses against tumor antigens, showing promising early results in an ongoing glioblastoma clinical trial (NCT04116658)

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“…PI3K is a dual-unit enzyme composed of a regulatory subunit (p85) and a catalytic subunit (p110). The interaction between p85 and phosphorylated tyrosine residues on the activated RTK alleviates inhibitory constraints on the catalytic function of p110 ( Fox et al, 2020 ; Wang et al, 2020 ; Tabnak et al, 2023 ). Consequently, this activation leads to the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3) within the cell membrane.…”

Section: Overview Of Pi3k/akt Signalingmentioning

confidence: 99%

Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer

Su,

Peng,

Liu

2024

Front. Cell Dev. Biol.

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The global challenge posed by cancer, marked by rising incidence and mortality rates, underscores the urgency for innovative therapeutic approaches. The PI3K/Akt signaling pathway, frequently amplified in various cancers, is central in regulating essential cellular processes. Its dysregulation, often stemming from genetic mutations, significantly contributes to cancer initiation, progression, and resistance to therapy. Concurrently, ferroptosis, a recently discovered form of regulated cell death characterized by iron-dependent processes and lipid reactive oxygen species buildup, holds implications for diseases, including cancer. Exploring the interplay between the dysregulated PI3K/Akt pathway and ferroptosis unveils potential insights into the molecular mechanisms driving or inhibiting ferroptotic processes in cancer cells. Evidence suggests that inhibiting the PI3K/Akt pathway may sensitize cancer cells to ferroptosis induction, offering a promising strategy to overcome drug resistance. This review aims to provide a comprehensive exploration of this interplay, shedding light on the potential for disrupting the PI3K/Akt pathway to enhance ferroptosis as an alternative route for inducing cell death and improving cancer treatment outcomes.

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Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics

Cited by 7 publications

References 225 publications

Exploring glioma heterogeneity through omics networks: from gene network discovery to causal insights and patient stratification

Exploring glioma heterogeneity through omics networks: from gene network discovery to causal insights and patient stratification

A Mimicry-Based Strategy Between Human and Commensal Antigens for the Development of a New Family of Immune Therapies for Cancer

Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer

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