PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?

Peng, Ying; Wang, Yuanyuan; Zhang, Cheng; Mei, Wuxuan; Zeng, Changchun

doi:10.3389/fonc.2022.819128

Cited by 272 publications

(222 citation statements)

References 121 publications

(127 reference statements)

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“…Activated mTORC1 signaling may trigger recurrent reprograming that helps escape from glycolytic addiction in cancer cell lines from various solid tumor types ( Pusapati et al, 2016 ). Recently, treatments targeting PI3K/AKT/mTOR and mTORC1 pathways have emerged as promising strategies in cancer therapeutics ( Yang et al, 2019 ; Peng et al, 2022 ). Epithelial–mesenchymal transition (EMT) is a process that the majority of tumors have gone through during tumor progression.…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas

et al. 2022

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Gliomas, a type of primary brain tumor, have emerged as a threat to global mortality due to their high heterogeneity and mortality. A low-grade glioma (LGG), although less aggressive compared with glioblastoma, still exhibits high recurrence and malignant progression. Ubiquitination is one of the most important posttranslational modifications that contribute to carcinogenesis and cancer recurrence. E3-related genes (E3RGs) play essential roles in the process of ubiquitination. Yet, the biological function and clinical significance of E3RGs in LGGs need further exploration. In this study, differentially expressed genes (DEGs) were screened by three differential expression analyses of LGG samples from The Cancer Genome Atlas (TCGA) database. DEGs with prognostic significance were selected by the univariate Cox regression analysis and log-rank statistical test. The LASSO-COX method was performed to identify an E3-related prognostic signature consisting of seven genes AURKA, PCGF2, MAP3K1, TRIM34, PRKN, TLE3, and TRIM17. The Chinese Glioma Genome Atlas (CGGA) dataset was used as the validation cohort. Kaplan–Meier survival analysis showed that LGG patients in the low-risk group had significantly higher overall survival time than those in the high-risk group in both TCGA and CGGA cohorts. Furthermore, multivariate Cox regression analysis revealed that the E3RG signature could be used as an independent prognostic factor. A nomogram based on the E3RG signature was then established and provided the prediction of the 1-, 3-, and 5-year survival probability of patients with LGGs. Moreover, DEGs were analyzed based on the risk signature, on which function analyses were performed. GO and KEGG analyses uncovered gene enrichment in extracellular matrix–related functions and immune-related biological processes in the high-risk group. GSEA revealed high enrichment in pathways that promote tumorigenesis and progression in the high-risk group. Furthermore, ESTIMATE algorithm analysis showed a significant difference in immune and stroma activity between high- and low-risk groups. Positive correlations between the risk signature and the tumor microenvironment immune cell infiltration and immune checkpoint molecules were also observed, implying that patients with the high-risk score may have better responses to immunotherapy. Overall, our findings might provide potential diagnostic and prognostic markers for LGG patients and offer meaningful insight for individualized treatment.

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Section: Discussionmentioning

confidence: 99%

“…Recently, treatments targeting PI3K/AKT/mTOR and mTORC1 pathways have emerged as promising strategies in cancer therapeutics (Yang et al, 2019;Peng et al, 2022). Epithelial-mesenchymal transition (EMT) is a process that the majority of tumors have gone through during tumor progression.…”

Section: )mentioning

confidence: 99%

Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas

et al. 2022

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“…Targeting PI3K/AKT/mTOR pathway is considered one of the most signi cant approaches used as anticancer strategy. There are many PI3K/AKT/mTOR pathway-inhibiting compounds that are commercially available, and the barrier to their effectiveness is the body's resistance to these medications 40 . Down regulating the expression of proteins involved in PI3K/AKT/mTOR pathway leads to cell cycle arrest and apoptosis 41 .…”

Section: Discussionmentioning

confidence: 99%

Anticancer activities of Saudi Juniperus procera extracts and their effects on the regulatory mechanisms in controlling growth of human cancerous cells

Al-Zahrani

Ibraheem

El-Senduny

2022

Preprint

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Cancer is one of the most distributed diseases in the world, which has been associated with a high number of mortalities compared to other diseases. Compared to traditional cancer treatment methods such as chemotherapy and radiotherapy, anti-cancer medicinal plants are mor safer due to their minimum side effects. The Juniperus procera plant is one of medicinal plants used in traditional Saudi medicine, and its extract is used to treat many diseases including cancer. In this study, we investigated the anticancer impacts of J. procera extracts and their potential anticancer activities on breast, ovarian and liver cancers with the focus on the first type. Phytochemical analysis revealed that the fruit extract had higher amount of total phenolics while the leaf extract was richer in flavonoids. The fruit extract showed more antioxidant and cytotoxicity activities against breast, ovarian, and liver cancers. MCF-7 and MDA-MB-231, breast cancer cell lines were further investigated using the fruit extract. Both cell lines were arrested in S phase and G1 phase, respectively. Nuclear fragmentations and apoptosis were triggered in both cell lines. ROS was increased and the cell migration was inhibited. PI3K/Akt/mTOR pathway was down regulated. Aromatase gene expression was decreased in MCF-7 and increased in MDA-MB-231. Both extracts were selective toward cancer cells rather than the normal cells (SI > 2). Fruit and leaf extracts have significant antitumor activities, and such activity was more pronounced in the fruit extract than leaf extract. This study highlights the importance of J. procera leaf and fruit as an anti-cancer.

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“…In addition, radiation resistance and chemotherapy resistance lead to unsatisfactory treatment effects in some patients [ 146 ]. Due to the prominent role of the PI3K/AKT/mTOR pathway in cell proliferation and survival, inhibitors of this pathway are anticipated to be effective treatments for NPC [ 147 ]. Preclinical trials showed that PI3K inhibitors decreased cell proliferation, decreased xenograft tumour growth, and increased radiosensitivity [ 148 ].…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Small biomarkers with massive impacts: PI3K/AKT/mTOR signalling and microRNA crosstalk regulate nasopharyngeal carcinoma

Deng

et al. 2022

Biomark Res

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Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumours of the head and neck in Southeast Asia and southern China. The Phosphatidylinositol 3-kinase/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway is involved in processes related to tumour initiation/progression, such as proliferation, apoptosis, metastasis, and drug resistance, and is closely related to the clinicopathological features of NPC. In addition, key genes involved in the PI3K/AKT/mTOR signalling pathway undergo many changes in NPC. More interestingly, a growing body of evidence suggests an interaction between this signalling pathway and microRNAs (miRNAs), a class of small noncoding RNAs. Therefore, in this review, we discuss the interactions between key components of the PI3K/AKT/mTOR signalling pathway and various miRNAs and their importance in NPC pathology and explore potential diagnostic biomarkers and therapeutic targets.

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PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?

Cited by 272 publications

References 121 publications

Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas

Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas

Anticancer activities of Saudi Juniperus procera extracts and their effects on the regulatory mechanisms in controlling growth of human cancerous cells

Small biomarkers with massive impacts: PI3K/AKT/mTOR signalling and microRNA crosstalk regulate nasopharyngeal carcinoma

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