The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions DOI Creative Commons
Huimin Yuan, Ruochen Xu, Senlin Li

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, predominantly associated with chronic hepatitis B virus (HBV) and C (HCV) infections. These infections drive persistent liver inflammation, culminating in cellular dysregulation, fibrosis, cancer. Despite advancements targeted therapies, drug resistance the lack reliable biomarkers for patient stratification still terribly hinder treatment viral HCC. To this end, review delves into intricate mechanisms underlying malignant transformation to HCC, including integration, genomic instability, epigenetic modifications, oxidative stress, gut microbiota dysbiosis, immune escape, abnormal signaling pathways, highlighting their complex interactions synergies. Cutting-edge preclinical clinical HCC management, lifestyle immunotherapies, gene-based approaches, innovative treatments, are further investigated, particular priority given therapeutic potential future applications overcoming current limitations. By synthesizing recent scientific insights, aims deepen understanding pathogenesis context hepatitis, paving way novel targets personalized strategies, ultimately improving outcomes.

Language: Английский

PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer DOI Creative Commons
Antonino Glaviano, Aaron Song Chuan Foo, Hiu Yan Lam

et al.

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

Citations

834
PI3K/AKT signaling pathway: Molecular mechanisms and therapeutic potential in depression DOI Creative Commons
Ningning Guo, Xin Wang,

Muran Xu

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107300 - 107300

Published: July 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.

Language: Английский

Citations

34
Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets DOI Open Access
Greta Pessino, Claudia Scotti, Maristella Maggi

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 901 - 901

Published: Feb. 23, 2024

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, genetic factors. No specific alterations are unequivocally linked to tumorigenesis. Current standard therapies surgical options, systemic chemotherapy, kinase inhibitors, like sorafenib regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint such as atezolizumab pembrolizumab, show efficacy, combination enhance clinical responses. Despite this, the treatment of (HCC) remains challenge, complex tumor ecosystem immunosuppressive microenvironment associated with it hamper efficacy available therapeutic approaches. This review explores current advanced approaches treat HCC, considering both known new potential targets, especially derived from proteomic analysis, which is today considered most approach. Exploring novel strategies, this discusses antibody drug conjugates (ADCs), chimeric antigen receptor T-cell therapy (CAR-T), engineered antibodies. It then reports systematic analysis main ligand/receptor pairs molecular pathways reported be overexpressed cells, highlighting their limitations. Finally, TGFβ, one targets microenvironment.

Language: Английский

Citations

21
Hepatocellular carcinoma: signaling pathways and therapeutic advances DOI Creative Commons

Jiaojiao Zheng,

Siying Wang, Lei Xia

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 6, 2025

Abstract Liver cancer represents a major global health concern, with projections indicating that the number of new cases could surpass 1 million annually by 2025. Hepatocellular carcinoma (HCC) constitutes around 90% liver and is primarily linked to factors incluidng aflatoxin, hepatitis B (HBV) C (HCV), metabolic disorders. There are no obvious symptoms in early stage HCC, which often leads delays diagnosis. Therefore, HCC patients usually present tumors advanced incurable stages. Several signaling pathways dis-regulated cause uncontrolled cell propagation, metastasis, recurrence HCC. Beyond frequently altered therapeutically targeted receptor tyrosine kinase (RTK) involved differentiation, telomere regulation, epigenetic modification stress response also provide therapeutic potential. Investigating key their inhibitors pivotal for achieving advancements management At present, primary approaches (TKI), immune checkpoint (ICI), combination regimens. New trials investigating therapies involving ICIs TKIs or anti-VEGF (endothelial growth factor) therapies, as well combinations two immunotherapy The outcomes these expected revolutionize across all Here, we here comprehensive review cellular pathways, potential, evidence derived from late-stage clinical discuss concepts underlying earlier trials, biomarker identification, development more effective therapeutics

Language: Английский

Citations

16
Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence DOI Creative Commons
Muhammad Tufail, Canhua Jiang, Ning Li

et al.

Military Medical Research, Journal Year: 2025, Volume and Issue: 12(1)

Published: Feb. 11, 2025

Abstract Cancer recurrence, driven by the phenomenon of tumor dormancy, presents a formidable challenge in oncology. Dormant cancer cells have ability to evade detection and treatment, leading relapse. This review emphasizes urgent need comprehend dormancy its implications for recurrence. Despite notable advancements, significant gaps remain our understanding mechanisms underlying lack reliable biomarkers predicting provides comprehensive analysis cellular, angiogenic, immunological aspects dormancy. It highlights current therapeutic strategies targeting dormant cells, particularly combination therapies immunotherapies, which hold promise preventing By elucidating these proposing innovative research methodologies, this aims deepen ultimately facilitating development more effective recurrence improving patient outcomes.

Language: Английский

Citations

3
Prunin: An Emerging Anticancer Flavonoid DOI Open Access
Juie Nahushkumar Rana, Sohail Mumtaz

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2678 - 2678

Published: March 16, 2025

Despite the substantial advances in cancer therapies, developing safe and effective treatment methodologies is critical. Natural (plant-derived compounds), such as flavonoids, might be crucial a methodology without toxicity toward healthy tissues. Prunin flavonoid with potential to used biomedical applications. has yet undergo thorough scientific research, its precise molecular mechanisms of action remain largely unexplored. This review summarizes therapeutic prunin for first time, focusing on underlying an anticancer compound. gained significant attention due antioxidant, anti-inflammatory, effects. aims unlock how functions at level exert effects, primarily modulating key cellular pathways. Furthermore, we have discussed prunin’s adjunctive therapy conventional treatments, highlighting ability strengthen responses while decreasing drug resistance. Moreover, discussion probes into innovative delivery methods, particularly nanoformulations, that address bioavailability, solubility, stability limitations optimize application. By providing comprehensive analysis properties, this stimulate further exploration using agent, thereby progressing development targeted, selective, safe, methods.

Language: Английский

Citations

3
Hepatocellular Carcinoma: Latest Research in Pathogenesis, Detection and Treatment DOI Open Access
Beatrice Foglia, Cristian Turato, Stefania Cannito

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12224 - 12224

Published: July 31, 2023

The most common form of primary liver malignancy is hepatocellular carcinoma (HCC) [...]

Language: Английский

Citations

34
Targeting EGFR/PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma DOI Creative Commons

Jieun Bang,

Mihyeon Jun,

S. J. Lee

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(8), P. 2130 - 2130

Published: Aug. 14, 2023

Hepatocellular carcinoma (HCC) poses a significant global health concern, with its incidence steadily increasing. The development of HCC is multifaceted, multi-step process involving alterations in various signaling cascades. In recent years, progress has been made understanding the molecular pathways that play central roles hepatocarcinogenesis. particular, EGFR/PI3K/AKT/mTOR pathway garnered renewed attention from both basic and clinical researchers. Preclinical studies vitro vivo have shown effectiveness targeting key components this human cells. Thus, these small molecule inhibitors holds promise as potential therapeutic option for patients HCC. review, we explore advancements role assess cascade strategy therapy based on preclinical studies.

Language: Английский

Citations

30
Targeting PI3K/AKT/mTOR Signaling to Overcome Drug Resistance in Cancer DOI
Muhammad Tufail,

Wendong Wan,

Canhua Jiang

et al.

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 396, P. 111055 - 111055

Published: May 17, 2024

Language: Английский

Citations

13
Immunometabolism in cancer: basic mechanisms and new targeting strategy DOI Creative Commons

Ranran Su,

Yingying Shao,

Manru Huang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 16, 2024

Abstract Maturing immunometabolic research empowers immune regulation novel approaches. Progressive metabolic adaptation of tumor cells permits a thriving microenvironment (TME) in which always lose the initial killing capacity, remains an unsolved dilemma even with development checkpoint therapies. In recent years, many studies on immunometabolism have been reported. The may facilitate anti-tumor immunotherapy from recurrent crosstalk between metabolism and immunity. Here, we discuss clinical core signaling pathways their inhibitors or agonists, as well specific functions these regulating immunity metabolism, some identified checkpoints. Understanding comprehensive advances helps to revise status quo cancer treatment.

Language: Английский

Citations

12