Chinese Journal of Natural Medicines, Journal Year: 2025, Volume and Issue: 23(3), P. 346 - 353
Published: March 1, 2025
Language: Английский
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
823
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
32
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
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
12
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
33
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
Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 396, P. 111055 - 111055
Published: May 17, 2024
Language: Английский
Citations
13
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
Cancer Research, Journal Year: 2024, Volume and Issue: 84(15), P. 2417 - 2431
Published: May 8, 2024
Abstract Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes suppress could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse human liver cancer identified lecithin cholesterol acyltransferase (LCAT) as most highly estrogen-upregulated gene a biomarker favorable prognosis. LCAT upregulation inhibited vitro vivo mediated estrogen-induced suppression ESR1-dependent manner. facilitated high-density lipoprotein production uptake via LDLR SCARB1 pathways. Consistently, high HDL-C levels corresponded prognosis patients. The enhanced absorption induced by impaired SREBP2 maturation, which ultimately suppressed biosynthesis dampened cell proliferation. alone growth comparably cholesterol-lowering drug lovastatin, SREBF2 overexpression abolished inhibitory activity LCAT. Clinical observations cross-analyses multiple databases confirmed correlation elevated reduced synthesis patient Furthermore, deficiency mimicked whereas abrogated tumor growth–promoting ovariectomy HCC-bearing female mice. Most importantly, delayed development subcutaneous tumors nude mice, synergized with lenvatinib eradicate orthotopic tumors. Collectively, this study reveals estrogen upregulates maintain homeostasis dampen hepatocarcinogenesis. represent potential prognostic therapeutic biomarkers for targeting strategy treating HCC. Significance: mediates sex differences hepatocellular reducing through activation LCAT/HDL-C axis, providing strategies improving prevention, prognosis, treatment.
Language: Английский
Citations
10
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
2