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

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 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.

Language: Английский

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Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 24, 2021

Circular RNAs (circRNAs), covalently closed noncoding RNAs, are widely expressed in eukaryotes and viruses. They can function by regulating target gene expression, linear RNA transcription protein generation. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays key roles many biological cellular processes, such as cell proliferation, growth, invasion, migration, angiogenesis. It also a pivotal role cancer progression. Emerging data suggest that the circRNA/PI3K/AKT axis modulates expression of cancer-associated genes thus regulates tumor Aberrant regulation circRNAs is significantly associated with clinicopathological characteristics an important functions. In this review, we summarized functions PI3K-AKT-related vitro vivo assessed their associations characteristics. We further discussed diagnosis, prognostication, treatment cancers.

Language: Английский

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Advances in the role of STAT3 in macrophage polarization

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 4, 2023

The physiological processes of cell growth, proliferation, differentiation, and apoptosis are closely related to STAT3, it has been demonstrated that aberrant STAT3 expression an impact on the onset progression a number inflammatory immunological disorders, fibrotic diseases, malignancies. In order produce necessary biological effects, macrophages (M0) can be polarized into pro-inflammatory (M1) anti-inflammatory (M2) types in response various microenvironmental stimuli. signaling is involved macrophage polarization, research effect polarization gained attention recent years. provide references for treatment investigation disorders this review compiles pertinent pathways associated with from many fundamental studies.

Language: Английский

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Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13381 - 13381

Published: Aug. 29, 2023

Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong terminal stage disease, i.e., type 2 diabetes (T2DM). The World Health Organization predicts that will be seventh leading cause death by 2030. Although many antidiabetic medicines have been successfully developed in recent years, such as GLP-1 receptor agonists SGLT-2 inhibitors, single-target drugs are gradually failing to meet therapeutic requirements owing individual variability, diversity pathogenesis, organismal resistance. Therefore, there remains need investigate pathogenesis T2DM more depth, identify targets, provide improved glycemic control solutions. This review presents an overview mechanisms action development latest agents targeting years. It also discusses emerging target-based therapies new targets emerged within last three aim our theoretical basis for further advancement targeted T2DM.

Language: Английский

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

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1848 - 1848

Published: Feb. 3, 2024

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

Language: Английский

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The implications of FASN in immune cell biology and related diseases

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 25, 2024

Abstract Fatty acid metabolism, particularly fatty synthesis, is a very important cellular physiological process in which nutrients are used for energy storage and biofilm synthesis. As key enzyme the synthase (FASN) receiving increasing attention. Although previous studies on FASN have mainly focused various malignancies, many recently reported that regulates survival, differentiation, function of immune cells, subsequently participates occurrence development immune-related diseases. However, few to date systematically summarized molecular mechanisms cell biology related In this review, we discuss regulatory effect progress research implications Understanding diseases can offer insights into novel treatment strategies clinical

Language: Английский

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Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 11, 2024

Novel therapeutic agents in clinical trials offer a paradigm shift the approach to battling this prevalent and destructive disease, area of cancer therapy is on precipice trans formative revolution. Despite importance tried-and-true treatments like surgery, radiation, chemotherapy, disease continues evolve adapt, making new, more potent methods necessary. The field currently witnessing emergence wide range innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, vaccines, utilizes host's immune system selectively target eradicate malignant cells while minimizing harm normal tissue. development targeted medicines kinase inhibitors monoclonal antibodies has allowed for less harmful approaches treating cancer. With help genomics molecular profiling, "precision medicine" customizes therapies each patient's unique genetic makeup maximize efficacy unwanted side effects. Epigenetic therapies, metabolic interventions, radio-pharmaceuticals, an increasing emphasis combination with synergistic effects further broaden landscape. Multiple-stage are essential determining safety these novel drugs, allowing patients gain access also furthering scientific understanding. future rife promise, as integration artificial intelligence big data potential revolutionize early detection prevention. Collaboration among researchers, healthcare providers, active involvement remain bedrock ongoing battle against In conclusion, dynamic evolving landscape provides hope improved treatment outcomes, emphasizing patient-centered, data-driven, ethically grounded we collectively strive towards cancer-free world.

Language: Английский

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Therapeutic advances of targeting receptor tyrosine kinases in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 14, 2024

Abstract Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression certain RTKs, are critical creating environments conducive tumor development. Following discovery, extensive research has revealed how RTK dysregulation contributes oncogenesis, with many subtypes showing dependency on aberrant signaling for proliferation, survival progression. These findings paved the way targeted therapies that aim inhibit crucial biological pathways cancer. As result, RTKs emerged as primary targets anticancer therapeutic Over past two decades, this led synthesis validation numerous small molecule kinase inhibitors (TKIs), now effectively utilized treating various types. In manuscript we provide comprehensive understanding context We explored alterations specific receptors across different malignancies, special dedicated examination current inhibitors, highlighting potential therapies. By integrating latest evidence, seek elucidate pivotal biology efficacy inhibition promising treatment outcomes.

Language: Английский

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New Insights into Antioxidant Peptides: An Overview of Efficient Screening, Evaluation Models, Molecular Mechanisms, and Applications

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 203 - 203

Published: Feb. 5, 2024

Antioxidant peptides are currently a hotspot in food science, pharmaceuticals, and cosmetics. In different fields, the screening, activity evaluation, mechanisms, applications of antioxidant pivotal areas research. Among these topics, efficient screening stands at forefront cutting-edge To this end, with novel technologies has significantly accelerated research process, gradually replacing traditional approach. After screened identified, time-consuming evaluation is another indispensable procedure, especially vivo models. Cellular rodent models have been widely used for whilst non-rodent provide an solution, even potential high-throughput screening. Meanwhile, further molecular mechanisms can elucidate essence underlying activity, which related to several signaling pathways, including Keap1-Nrf2/ARE, mitochondria-dependent apoptosis, TGF-β/SMAD, AMPK/SIRT1/PGC-1α, PI3K/Akt/mTOR, NF-κB. Last but not least, broad manufacture, therapy, cosmetics industry, requires systematic review. This review introduces peptides, categorized new vision. A wide range assays, encompassing cellular models, as well provided comprehensive manner. addition, recent advances analyzed specific cases. Finally, production, systematically reviewed.

Language: Английский

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Augmented ERO1α upon mTORC1 activation induces ferroptosis resistance and tumor progression via upregulation of SLC7A11

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: April 13, 2024

The dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood. Endoplasmic reticulum oxidoreductase alpha (ERO1α) expression mTORC1-activated mouse embryonic fibroblasts, cancer cells, laryngeal squamous cell carcinoma (LSCC) clinical samples was examined by quantitative real-time PCR (qRT-PCR), western blotting, immunofluorescence (IF), immunohistochemistry. Extensive vitro vivo experiments were carried out determine ERO1α its downstream target, member 11 solute carrier family 7 (SLC7A11), mTORC1-mediated proliferation, angiogenesis, resistance, tumor growth. regulatory mechanism on SLC7A11 investigated via RNA-sequencing, cytokine array, an enzyme-linked immunosorbent assay, qRT-PCR, IF, luciferase reporter chromatin immunoprecipitation assay. combined therapeutic effect inhibition inducer imidazole ketone erastin (IKE) cells evaluated using line-derived xenografts, LSCC organoids, patient-derived xenograft models. is functional mTORC1. Elevated induced exerted pro-oncogenic roles upregulation SLC7A11. Mechanically, stimulated transcription activating interleukin-6 (IL-6)/signal transducer activator 3 (STAT3) pathway. Moreover, with treatment IKE exhibited synergistic antitumor effects tumors. ERO1α/IL-6/STAT3/SLC7A11 pathway crucial for growth, combining inducers novel effective mTORC1-related

Language: Английский

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