PTEN Alterations and Their Role in Cancer Management: Are We Making Headway on Precision Medicine?

Fusco, Nicola; Sajjadi, Elham; Venetis, Konstantinos; Gaudioso, Gabriella; Lopez, Gianluca; Corti, Chiara; Guerini-Rocco, Elena; Criscitiello, Carmen; Malapelle, Umberto; Invernizzi, Marco

doi:10.3390/genes11070719

Cited by 92 publications

(66 citation statements)

References 111 publications

(174 reference statements)

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“…While this combination of genes may lead to the inhibition of liver cancer development, changes to individual genes, such as the inhibition of the tumor suppressor gene Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) may have the potential to increase the development of other neoplasms. PTEN acts on the phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway and is one of the most commonly disrupted tumor suppressors in human cancer [ 46 ]. Its inhibition or loss is considered a founder genetic event for the induction and progression of tumor development [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Continual Consumption of Origanum vulgare on Liver Transcriptomics

Bajagai

Radovanović

Steel

et al. 2021

Animals

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Pathogen control is re-emerging as a significant challenge to the health of both humans and animals. The livestock industry is in the process of massively replacing in-feed antibiotics with organic production friendly plant-based products. Nutrigenomics as a science of the effects of food constituents on gene expression is shedding more light on both benefits and detrimental side-effects of feed additive prolonged consumption on the host, indicating the need to understand the feed–host interactions and their influence on the host disease profile. In this study, we investigated the effects of 2% oregano powder supplementation on the liver gene expression in healthy male broilers from the hatch to 6 weeks of age. Deep RNAseq was performed on average 113.3 million paired and quality trimmed sequences per sample and four samples for the control and treatment each. The results demonstrate the severity of oregano effect on liver gene expression with substantial modifications in steroid hormone regulation, fat and carbohydrate metabolism alterations and strong influence on the host disease and function profile. Oregano supplementation was able to interfere with the transcriptional effects of a range of registered drugs and to significantly transcriptionally inhibit a range of cancer disease categories including liver cancer, and to modify fat and carbohydrate metabolism.

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Section: Discussionmentioning

confidence: 99%

The Effects of Continual Consumption of Origanum vulgare on Liver Transcriptomics

Bajagai

Radovanović

Steel

et al. 2021

Animals

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“…PTEN regulates PI3K via dephosphorylating phosphatidylinositol-3, 4, 5-trisphosphate (PIP3). The loss of or gain in function is seen in several cancers including breast, brain and prostate [ 17 , 18 ]. Increased PI3K signaling and tumorigenesis is observed in PTEN knock-in mice with PTEN mutations [ 18 ].…”

Section: Signaling Molecules and Factors Contributing To Pi3k Inhimentioning

confidence: 99%

PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects

Mishra

Patel

Alanazi

et al. 2021

IJMS

150

105

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The phospatidylinositol-3 kinase (PI3K) pathway is a crucial intracellular signaling pathway which is mutated or amplified in a wide variety of cancers including breast, gastric, ovarian, colorectal, prostate, glioblastoma and endometrial cancers. PI3K signaling plays an important role in cancer cell survival, angiogenesis and metastasis, making it a promising therapeutic target. There are several ongoing and completed clinical trials involving PI3K inhibitors (pan, isoform-specific and dual PI3K/mTOR) with the goal to find efficient PI3K inhibitors that could overcome resistance to current therapies. This review focuses on the current landscape of various PI3K inhibitors either as monotherapy or in combination therapies and the treatment outcomes involved in various phases of clinical trials in different cancer types. There is a discussion of the drug-related toxicities, challenges associated with these PI3K inhibitors and the adverse events leading to treatment failure. In addition, novel PI3K drugs that have potential to be translated in the clinic are highlighted.

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“…Upon complete activation, Akt induces multiple downstream cytosolic and nuclear effectors. This mechanism, considered as the “core” of cell survival and cell cycle progression, is turned off by several phosphatases (PTEN, TSC1, TSC2, and LKB1) that dephosphorylate mTORC1 and PIP3 ( 29 – 31 ) ( Figure 1 ).…”

Section: Biology and Actionability Of Pik3ca Mutatmentioning

confidence: 99%

PIK3CA Mutations as a Molecular Target for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer

et al. 2021

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Despite the significant achievements in the diagnosis and treatment of metastatic breast cancer (MBC), this condition remains substantially an incurable disease. In recent years, several clinical studies have aimed to identify novel molecular targets, therapeutic strategies, and predictive biomarkers to improve the outcome of women with MBC. Overall, ~40% of hormone receptor (HR)+/HER2− MBC cases harbor alterations affecting the (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. This pathway is a major target in oncogenesis, as it regulates growth, proliferation, cell survival, and angiogenesis. Lately, the pharmacologic targeting of PIK3CA in HR+/HER2− MBC has shown significant benefits after the occurrence of endocrine therapy resistance. The orally available α-selective PIK3CA inhibitor, alpelisib, has been approved in this setting. To perform an optimal patients' selection for this drug, it is crucial to adopt a tailored methodology. Clinically relevant PIK3CA alterations may be detected in several biospecimens (e.g. tissue samples and liquid biopsy) using different techniques (e.g. real-time PCR and next-generation sequencing). In this study, we provide an overview of the role of PIK3CA in breast cancer and of the characterization of its mutational status for appropriate clinical management.

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PTEN Alterations and Their Role in Cancer Management: Are We Making Headway on Precision Medicine?

Cited by 92 publications

References 111 publications

The Effects of Continual Consumption of Origanum vulgare on Liver Transcriptomics

The Effects of Continual Consumption of Origanum vulgare on Liver Transcriptomics

PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects

PIK3CA Mutations as a Molecular Target for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer

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