PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Авг. 18, 2023

Abstract The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, growth, and cycle progression. Growth factor signalling to transcription factors the PAM axis regulated by multiple cross-interactions with several other pathways, dysregulation of can predispose cancer development. most frequently activated human often implicated resistance anticancer therapies. Dysfunction components this such as hyperactivity PI3K, loss function PTEN, gain-of-function AKT, are notorious drivers treatment disease progression cancer. In review we highlight major dysregulations cancer, discuss results AKT mTOR inhibitors monotherapy co-administation antineoplastic agents clinical trials strategy for overcoming resistance. Finally, mechanisms targeted therapies, including immunology immunotherapies also discussed.

Язык: Английский

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Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy

Molecular Biomedicine, Год журнала: 2022, Номер 3(1)

Опубликована: Дек. 21, 2022

The PI3K/AKT/mTOR and RAF/MEK/ERK pathways are commonly activated by mutations chromosomal translocation in vital targets. signaling pathway is dysregulated nearly all kinds of neoplasms, with the component this alternations. cascades used to conduct from cell surface nucleus mediate gene expression, cycle processes apoptosis. RAS, B-Raf, PI3K, PTEN frequent upstream alternative sites. These resulted growth downregulated two interact each other participate tumorigenesis. alterations suppress activity via AKT phosphorylation RAS inhibition. Several inhibitors targeting major components these have been supported FDA. Dozens agents attracted great attention assessed clinical trials. combination small molecular traditional regimens has also explored. Furthermore, dual provide new insight into antitumor activity. This review will further comprehensively describe genetic normal patients tumor discuss role targeted malignant neoplasm therapy. We hope promote a comprehensive understanding facilitating tumors help direct drug selection for

Язык: Английский

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The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2652 - 2652

Опубликована: Янв. 31, 2023

Hepatocellular carcinoma (HCC) is one of the leading causes cancer-related deaths in world. Metabolic reprogramming considered a new hallmark cancer, but it remains unclearly described HCC. The dysregulation PI3K/AKT/mTOR signaling pathway common HCC and is, therefore, topic further research concern developing novel target for liver cancer therapy. In this review, we illustrate mechanisms by which network accountable regulating cellular metabolism, including glucose lipid amino acid pyrimidine oxidative summarize ongoing clinical trials based on inhibition

Язык: Английский

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Glioblastoma Therapy: Past, Present and Future

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2529 - 2529

Опубликована: Фев. 21, 2024

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians researchers, no significant improvement in survival has achieved since Stupp protocol became standard care (SOC) 2005. Despite multimodality treatments, recurrence is almost universal with rates under 2 years after diagnosis. Here, we discuss recent progress our understanding GB pathophysiology, particular, importance glioma stem cells (GSCs), tumor microenvironment conditions, epigenetic mechanisms involved growth, aggressiveness recurrence. The discussion on therapeutic strategies first covers SOC treatment targeted therapies that shown to interfere different signaling pathways (pRB/CDK4/RB1/P16

Язык: Английский

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Targeting Breast Cancer: An Overlook on Current Strategies

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 3643 - 3643

Опубликована: Фев. 11, 2023

Breast cancer (BC) is one of the most widely diagnosed cancers and a leading cause death among women worldwide. Globally, BC second frequent first gynecological one, affecting with relatively low case-mortality rate. Surgery, radiotherapy, chemotherapy are main treatments for BC, even though latter often not aways successful because common side effects damage caused to healthy tissues organs. Aggressive metastatic BCs difficult treat, thus new studies needed in order find therapies strategies managing these diseases. In this review, we intend give an overview field, presenting data from literature concerning classification drugs used therapy treatment BCs, along clinical studies.

Язык: Английский

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Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1848 - 1848

Опубликована: Фев. 3, 2024

Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year.

Язык: Английский

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Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 3, 2024

Abstract Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as crucial contributor development, advancement, resistance This review article explores implications of PI3K in predictive, preventive, personalized medicine for BC. It emphasizes identification predictive biomarkers, such PIK3CA mutations, utility profiling guiding treatment decisions. The also discusses potential targeting preventive strategies customization therapy based on tumor stage, subtypes, genetic alterations. Overcoming inhibitors exploring combination therapies are addressed important considerations. While this field holds promise improving patient outcomes, further research clinical trials needed validate these approaches translate them into practice. Graphical

Язык: Английский

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The Potential Health Benefits of Gallic Acid: Therapeutic and Food Applications

Antioxidants, Год журнала: 2024, Номер 13(8), С. 1001 - 1001

Опубликована: Авг. 18, 2024

Gallic acid (GA), a phenolic found in fruits and vegetables, has been consumed by humans for centuries. Its extensive health benefits, such as antimicrobial, antioxidant, anticancer, anti-inflammatory, antiviral properties, have well-documented. GA's potent antioxidant capabilities enable it to neutralize free radicals, reduce oxidative stress, protect cells from damage. Additionally, GA exerts anti-inflammatory effects inhibiting inflammatory cytokines enzymes, making potential therapeutic agent diseases. It also demonstrates anticancer properties cancer cell growth promoting apoptosis. Furthermore, offers cardiovascular lowering blood pressure, decreasing cholesterol, enhancing endothelial function, which may aid the prevention management of This review covers chemical structure, sources, identification quantification methods, biological GA, along with its applications food. As research progresses, future appears promising, uses functional foods, pharmaceuticals, nutraceuticals aimed at improving overall preventing disease. However, ongoing innovation are necessary fully understand address current challenges, establish mainstay nutritional interventions.

Язык: Английский

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PI3K/AKT signaling pathway: Molecular mechanisms and therapeutic potential in depression

Pharmacological Research, Год журнала: 2024, Номер 206, С. 107300 - 107300

Опубликована: Июль 9, 2024

Depression is a serious global mental disorder. Numerous studies have found that depression may be closely related to decreased neurogenesis, neuroinflammation, neurotransmitter imbalance, and synaptic plasticity dysfunction. The pathogenesis of complex involves multiple signal transduction pathways molecular changes. PI3K/AKT pathway an essential signaling in neurons, which widely expressed emotion-related regions the brain. Therefore, play moderating role mood disorders. However, mechanism not been fully described. This review systematically summarized discussed its potential treatment depression. will help development antidepressants.

Язык: Английский

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

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Март 18, 2024

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

Язык: Английский

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