HER3: Toward the Prognostic Significance, Therapeutic Potential, Current Challenges, and Future Therapeutics in Different Types of Cancer

Cells, Journal Year: 2023, Volume and Issue: 12(21), P. 2517 - 2517

Published: Oct. 25, 2023

Human epidermal growth factor receptor 3 (HER3) is the only family member of EGRF/HER tyrosine kinases that lacks an active kinase domain (KD), which makes it obligate binding partner with other receptors for its oncogenic role. When HER3 activated in a ligand-dependent (NRG1/HRG) or independent manner, can bind to (the most potent HER2) regulate many biological functions (growth, survival, nutrient sensing, metabolic regulation, etc.) through PI3K–AKT–mTOR pathway. has been found promote tumorigenesis, tumor growth, and drug resistance different cancer types, especially breast non-small cell lung cancer. Given ubiquitous expression across solid tumors role oncogenesis resistance, there long effort target HER3. As cannot be targeted KD small-molecule inhibitors via conventional method, pharmaceutical companies have used various approaches, including blocking either ligand-binding extracellular dimerization receptors. The development treatment options anti-HER3 monoclonal antibodies, bispecific combination therapies showed limited clinical efficiency reasons. Recent reports not required receptors, raises doubt about efforts applicability HER3-antibodies treatment. Whereas HER3-directed antibody–drug conjugates potentiality treatment, these drugs are still under trial. currently understood model dimerization-induced signaling remains incomplete due absence crystal structure complexes, lines evidence suggest HER involves more than interaction two members. This review article will significantly expand our knowledge shed light on developing new generation fewer side effects current regimen patients.

Language: Английский

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Evolving CAR-T-Cell Therapy for Cancer Treatment: From Scientific Discovery to Cures

Cancers, Journal Year: 2023, Volume and Issue: 16(1), P. 39 - 39

Published: Dec. 20, 2023

In recent years, chimeric antigen receptor (CAR)-T-cell therapy has emerged as the most promising immunotherapy for cancer that typically uses patients’ T cells and genetically engineered them to target cells. Although improvements in CAR-T-cell have shown remarkable success treating hematological malignancies, heterogeneity tumor antigens immunosuppressive nature of microenvironment (TME) limits its efficacy solid tumors. Despite enormous efforts been made make more effective minimal side effects research needs be conducted regarding use clinic various other types cancer. The main concern is severe toxicities due cytokine release syndrome, whereas challenges are associated with complexity immune-suppressing TME, heterogeneity, difficulty cell trafficking, exhaustion, reduced cytotoxicity site. This review discussed latest discoveries strategies combination therapies, well their effectiveness different cancers. It also encompasses ongoing clinical trials; current therapeutic therapy, especially tumors; evolving treatment improve application therapy.

Language: Английский

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How the Western Diet Thwarts the Epigenetic Efforts of Gut Microbes in Ulcerative Colitis and Its Association with Colorectal Cancer

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 633 - 633

Published: May 29, 2024

Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks colon, leading to ulcer development, loss of colon function, and bloody diarrhea. The human gut ecosystem consists almost 2000 different species bacteria, forming a bioreactor fueled by dietary micronutrients produce bioreactive compounds, are absorbed our body signal distant organs. Studies have shown that Western diet, with fewer short-chain fatty acids (SCFAs), can alter microbiome composition cause host's epigenetic reprogramming. Additionally, overproduction H

Language: Английский

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Bridging the Gap in Cancer Research: Sulfur Metabolism of Leukemic Cells with a Focus on L-Cysteine Metabolism and Hydrogen Sulfide-Producing Enzymes

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 746 - 746

Published: June 24, 2024

Leukemias are cancers of the blood-forming system, representing a significant challenge in medical science. The development leukemia cells involves substantial disturbances within cellular machinery, offering hope search for effective selective treatments that could improve 5-year survival rate. Consequently, pathophysiological processes focus critical research. Enzymes such as cystathionine beta-synthase and sulfurtransferases like thiosulfate sulfurtransferase, 3-mercaptopyruvate gamma-lyase play vital role sulfur metabolism. These enzymes essential to maintaining homeostasis, providing robust antioxidant defenses, supporting cell division. Numerous studies have demonstrated cancerous can alter expression activity these enzymes, uncovering potential vulnerabilities or molecular targets cancer therapy. Recent laboratory research has indicated certain lines may exhibit changes patterns enzymes. Analysis scientific literature online datasets confirmed variations enzyme function specific leukemic compared normal leukocytes. This comprehensive review collects analyzes available information on lines, valuable insights identifying new pathways this field.

Language: Английский

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Mechanistic Intimate Insights into the Role of Hydrogen Sulfide in Alzheimer’s Disease: A Recent Systematic Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15481 - 15481

Published: Oct. 23, 2023

In the rapidly evolving field of Alzheimer's Disease (AD) research, intricate role Hydrogen Sulfide (H

Language: Английский

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Homocysteine and multiple health outcomes: an outcome-wide umbrella review of meta-analyses and Mendelian randomization studies

Advances in Nutrition, Journal Year: 2025, Volume and Issue: unknown, P. 100434 - 100434

Published: April 1, 2025

Elevated levels of homocysteine (Hcy) are associated with various health outcomes. We aimed to systematically assess the credibility and certainty evidence associations Hcy Hcy-lowering therapies retrieved observational meta-analyses examining between outcomes, interventional investigating outcomes related treatments, Mendelian Randomization (MR) studies exploring causal perform an umbrella review. A total 135 meta-analyses, 106 MR studies, 26 were included. Among 10 diseases/outcomes classified as highly suggestive; only one outcome (digestive tract cancer) was supported by convincing (class I; OR=1.27, 95% CI=1.16-1.40; P=6.79×10-7; I2=0, prediction interval excluding null, >1000 cases; P>0.1 for tests both small-study effects excess significance bias). In 5 presented robust (P<0.01, power>80%). 25 explored 7 had consistent results, indicating that elevated is causally increased risk these The 3 types collectively suggested association stroke further validated intervention showing folic acid significantly reduced stroke. For dementia colorectal cancer, in decreased disease risks meta-analyses. current review indicates a definitive role exposure solely exists context digestive cancer bias; however, may not be this disease. All three type support key factor, (specifically acid) serve effective REGISTRATION PROSPERO: CRD42024541335 STATEMENT OF SIGNIFICANCE: Previous systematic reviews has been summarized appraised randomization on or homocysteine-lowering range diseases (outcomes). Our takes full advantage respective strengths combining comparing findings explore potential importance implications clinical practice public health.

Language: Английский

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Deciphering the Potentials of Cardamom in Cancer Prevention and Therapy: From Kitchen to Clinic

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1166 - 1166

Published: Sept. 18, 2024

Cardamom (cardamum) is a spice produced from the seeds of several Elettaria and Amomum plants Zingiberaceae family. has been demonstrated to offer numerous benefits, including its antioxidant, antimicrobial, anti-inflammatory, other metabolic (anti-diabetic) properties, potential reduce cancer risk. Recently, researchers have extracted tested multiple phytochemicals cardamom assess their effectiveness against various types human malignancy. These studies indicated that can help overcome drug resistance standard chemotherapy protect chemotherapy-induced toxicity due scavenging properties. Furthermore, chemical compounds in cardamom, limonene, cymene, pinene, linalool, borneol, cardamonin, indole-3-carbinol, diindolylmethane, primarily target programmed cell death lignin-1 gene, which more prevalent cells than healthy cells. This review provides medicinal properties pharmacological uses cellular effects, therapeutic prevention treatment, as well use reducing improving overall health patients. Based on previous preclinical studies, shows significant an anti-cancer agent, but further exploration for clinical warranted diverse mechanisms action.

Language: Английский

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Taurine, alpha lipoic acid and vitamin B6 ameliorate the reduced developmental competence of immature mouse oocytes exposed to methylglyoxal

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 2, 2024

Advanced glycation end products (AGEs) are the final of Maillard reaction, formed through interaction carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve precursors for AGEs formation. Elevated levels MGO/AGEs observed in conditions like obesity, polycystic ovarian syndrome (PCOS), diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress acts an anti-glycation compound, preventing vitro accumulation. This study aimed to explore ameliorative effects micronutrient support (Taurine, ALA B6: TAB) on mouse oocytes challenged MGO. Our results indicate MGO reduces developmental competence, TAB supplementation improves maturation, fertilization, blastocyst rates. also restores cell lineage allocation, redox balance mitochondrial dysfunction MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes transsulfuration pathway, enhances their mRNA expression. However, does not rescue MGO-induced damage denuded oocytes, emphasizing supportive role cells. Overall, these findings suggest interventions may significant implications addressing reproductive dysfunctions associated elevated levels. highlights potential preserving competence COCs exposed stress, providing insights into mitigating impact quality outcomes.

Language: Английский

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Cr(VI) induced hepatocyte apoptosis through the CTH/H2S/Drp1 signaling pathway

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 950, P. 175332 - 175332

Published: Aug. 6, 2024

Language: Английский

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Bioinformatics analysis of the clinical value and potential mechanisms of CBS/H2S in Glioma through 1027 samples.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 23, 2024

Abstract Background Glioma is a highly malignant brain tumor with dismal prognosis, limiting effective treatment strategies. Thus,identifying the molecular mechanisms underlying tumor-related gene in glioma critical. Cystathionine beta-synthase (CBS), key kinase responsible for producing hydrogen sulfide (H2S) internally, has been implicated progression of tumors. However, there paucity studies focusing on CBS/H2S context glioma. Methods Data analysis mRNA-seq level was performed group 325 patients from Chinese Genome Altas (CGGA) database and 702 The Cancer (TCGA). TISIDB employed to explore connection between CBS expression immune cell infiltration levels.Furthermore, variation across multiple cancer types were examined by GEPIA database. Results showed enrichment low-grade gliomas IDH-mutant gliomas. Furthermore,CBS held great promise as biomarker glioblastoma an independent prognostic determinant affecting patients’ overall survival. Notably,the revealed inverse associations 28 distinct tumor-infiltrating lymphocytes (TILs).Moreover,CBS played pivotal role Pan-cancer,highlighting its significance Pan-cancer studies.

Language: Английский

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