PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications

Biology, Год журнала: 2023, Номер 12(5), С. 672 - 672

Опубликована: Апрель 29, 2023

High-risk human papillomaviruses (HR-HPVs) are the causal agents of cervical, anogenital and a subset head neck carcinomas (HNCs). Indeed, oropharyngeal cancers type HNC highly associated with HR-HPV infections constitute specific clinical entity. The oncogenic mechanism involves E6/E7 oncoprotein overexpression for promoting cell immortalization transformation, through downregulation p53 pRB tumor suppressor proteins, among other cellular targets. Additionally, proteins involved in PI3K/AKT/mTOR signaling pathway alterations. In this review, we address relationship between activation an emphasis on its therapeutic importance.

Язык: Английский

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Blockage of EGFR/AKT and mevalonate pathways synergize the antitumor effect of temozolomide by reprogramming energy metabolism in glioblastoma

Cancer Communications, Год журнала: 2023, Номер 43(12), С. 1326 - 1353

Опубликована: Ноя. 2, 2023

Abstract Background Metabolism reprogramming plays a vital role in glioblastoma (GBM) progression and recurrence by producing enough energy for highly proliferating tumor cells. In addition, metabolic is crucial growth immune‐escape mechanisms. Epidermal factor receptor ( EGFR ) amplification EGFR‐vIII mutation are often detected GBM cells, contributing to the malignant behavior. This study aimed investigate functional of pathway on fatty acid metabolism remodeling generation. Methods Clinical specimens were selected single‐cell RNA sequencing untargeted metabolomics analysis. A metabolism‐associated RTK‐fatty acid‐gene signature was constructed verified. MK‐2206 MK‐803 utilized block RTK mevalonate induced abnormal metabolism. Energy with activated monitored. The antitumor effect Osimertinib Atorvastatin assisted temozolomide (TMZ) analyzed an intracranial model vivo. Results high expression had characteristics lipid maintaining cholesterol levels, supported clinical samples. Inhibition EGFR/AKT pathways could remodel repressing tricarboxylic cycle modulating ATP production. Mechanistically, upregulated expressions acyl‐CoA synthetase short‐chain family member 3 (ACSS3), long‐chain (ACSL3), elongation‐related gene ELOVL elongase 2 (ELOVL2) NF‐κB‐dependent manner. Moreover, inhibition reduced level cell membranes, thereby affecting signal transduction pathway. Therefore, targeting enhanced TMZ cells animal models. Conclusions Our findings not only uncovered mechanism EGFR‐activated but also provided combinatorial therapeutic strategy management.

Язык: Английский

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Viruses in glioblastoma: an update on evidence and clinical trials

BJC Reports, Год журнала: 2024, Номер 2(1)

Опубликована: Апрель 19, 2024

Glioblastoma (GB) is a lethal and aggressive brain tumour. While molecular characteristics of GB studied extensively, the aetiology remains uncertain. The interest in exploring viruses as potential contributor to development stems from notion that are known play key role pathogenesis other human cancers such cervical cancer. Nevertheless, controversial.

Язык: Английский

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Glut-3 Gene Knockdown as a Potential Strategy to Overcome Glioblastoma Radioresistance

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2079 - 2079

Опубликована: Фев. 8, 2024

The hypoxic pattern of glioblastoma (GBM) is known to be a primary cause radioresistance. Our study explored the possibility using gene knockdown key factors involved in molecular response hypoxia, overcome GBM We used U87 cell line subjected chemical hypoxia generated by CoCl2 and exposed 2 Gy X-rays, as single or combined treatments, evaluated expression changes biomarkers Warburg effect, cycle control, survival identify best targets knocked-down, among those directly activated HIF-1α transcription factor. By this approach, glut-3 pdk-1 genes were chosen, effects their morpholino-induced silencing exploring proliferative rates modifications above-mentioned biomarkers. found that, after induced greater decrease proliferation, compared strong upregulation glut-1 ldha, sign restore anaerobic glycolysis pathway. Overall, offered better chance controlling use pyruvate proliferation rate reduction, suggesting it suitable target

Язык: Английский

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The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway

Cell Death and Disease, Год журнала: 2024, Номер 15(6)

Опубликована: Июнь 3, 2024

Abstract Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells plays an important role occurrence development human tumors. However, function mechanism heterogeneous nuclear ribonucleoprotein C (HNRNPC), RNA-binding protein m6A reader gliomas remains to be comprehensively extensively explored. Herein, we found that HNRNPC mRNA overexpression were associated with a poor prognosis for patients gliomas, based on data from TCGA, CGGA, TMAs. Biologically, knockdown markedly repressed phenotypes glioma vitro vivo, whereas ectopic expression had opposite effect. Integrative RNA sequencing MeRIP analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as downstream target HNRNPC. public datasets tissue microarrays (TMAs) indicated IRAK1 was prognosis, significantly biological behavior vitro. Mechanistically, maintains stability m6A-dependent manner, resulting activation mitogen-activated (MAPK) signaling pathway, which necessary glioma. Our findings demonstrate HNRNPC–IRAK1–MAPK axis crucial carcinogenic factor novel underlying upregulation, provides rationale therapeutically targeting epitranscriptomic modulators

Язык: Английский

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The combination of temozolomide and perifosine synergistically inhibit glioblastoma by impeding DNA repair and inducing apoptosis

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Июль 8, 2024

Abstract Temozolomide (TMZ) is widely utilized as the primary chemotherapeutic intervention for glioblastoma. However, clinical use of TMZ limited by its various side effects and resistance to chemotherapy. The present study revealed synergistic inhibition glioblastoma through combined administration perifosine. This combination therapy markedly diminished BRCA1 expression, resulting in suppression DNA repair mechanisms. Furthermore, perifosine elicited caspase-dependent apoptosis, decreasing cell viability proliferation. observed effect this on was validated vivo, evidenced substantial reduction xenograft growth following treatment with In recurrent glioma patients, higher expression associated worse prognosis, especially ones that received TMZ-treated. These findings underscore potent antitumor activity AKT inhibitor when suggest approach a promising strategy treatment.

Язык: Английский

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Emerging nanoplatforms towards microenvironment-responsive glioma therapy

Medical Oncology, Год журнала: 2025, Номер 42(2)

Опубликована: Янв. 15, 2025

Язык: Английский

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Quality by design enabled development & in-vitro assessment of a Nanoemulgel formulation for Nose-to-Brain delivery of Nintedanib for glioblastoma multiforme treatment

International Journal of Pharmaceutics, Год журнала: 2025, Номер unknown, С. 125632 - 125632

Опубликована: Апрель 1, 2025

Язык: Английский

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Camouflaging multifunctional nanoparticles with bacterial outer membrane for augmented chemodynamic/photothermal/starvation/chemo multimodal synergistic therapy of orthotopic glioblastoma

Chemical Engineering Journal, Год журнала: 2023, Номер 471, С. 144410 - 144410

Опубликована: Июнь 26, 2023

Язык: Английский

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Molecular mechanisms of tumour development in glioblastoma: an emerging role for the circadian clock

npj Precision Oncology, Год журнала: 2024, Номер 8(1)

Опубликована: Фев. 20, 2024

Abstract Glioblastoma is one of the most lethal cancers with current therapeutic options lacking major successes. This underlines necessity to understand glioblastoma biology on other levels and use these learnings for development new concepts. Mounting evidence in field circadian medicine points a tight interplay between disturbances system progression. The clock, an internal biological mechanism governing numerous physiological processes across 24-h cycle, also plays pivotal role regulationg key cellular functions, including DNA repair, cell cycle progression, apoptosis. These are integral tumour response therapy. Disruptions rhythms can influence growth, invasion, treatment patients. In this review, we explore robust association cancer hallmarks within context glioblastoma. We further discuss impact clock eight shown previously link molecular different cancers, summarize putative proteins rhythm chronotherapy By unravelling mechanisms behind intricate connections researchers pave way identification potential targets, innovative strategies personalized approaches. conclusion, review underscores significant advancement understanding future therapies glioblastoma, ultimately leading enhanced outcomes

Язык: Английский

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