The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Sept. 7, 2022

Abstract As our understanding of the mechanisms cancer treatment has increased, a growing number studies demonstrate pathways through which DNA damage repair (DDR) affects immune system. At same time, varied response patients to checkpoint blockade (ICB) therapy prompted discovery various predictive biomarkers and study combination therapy. Here, investigation explores interactions involved in therapy, accompanied by review that summarizes currently identified promising predictors inhibitors (ICIs) are useful for classifying oncology patients. In addition, this work, discusses immunogenicity several components tumor microenvironment, serves illustrate mechanism higher rates improved efficacy DDR (DDRi) with ICIs achieved.

Language: Английский

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Precision Oncology, Signaling Pathways Reprogramming and Targeted Therapy: A Holistic Approach to Molecular Cancer Therapeutics

Published: Jan. 8, 2025

Cancer is a fatal genetic disease involving unregulated cell growth and proliferation with varying underlying complexities including immune evasion, treatment resistance recurrence, optimized required for proper cure. Molecular studies have revealed that tumors are extremely heterogeneous in nature, leading to the complexity of cancer development, which ultimately linked its machinery. It would require effective targeting dysregulated molecular mechanisms factors, regulatory proteins, adhesion molecules, molecules system mainly driven by alterations tumor suppressor genes oncogenes may vary among different types. Importantly, patients same type respond differently available treatments, indicating need patient-specific options. Thus, in-depth genomic patients’ needed fully understand determinants initiation progression targeted therapy. Precision oncology has evolved as form therapy focused on profiling identify involved manifestation tailored individualized disease. Accordingly, there been great developments formulation production anticancer agents recent years owing advances technologies enabling precise oncogenic pathways progression. This article aims briefly explain foundations frontiers precision context advancements tools techniques associated process assess scope importance realizing intended goals.

Language: Английский

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Cancer Initiation and Progression: A Comprehensive Review of Carcinogenic Substances, Anti-Cancer Therapies, and Regulatory Frameworks

Asian Journal of Research in Biochemistry, Journal Year: 2024, Volume and Issue: 14(4), P. 111 - 125

Published: June 22, 2024

Cancer is a multifaceted disease influenced by genetic mutations and environmental factors, including exposure to carcinogens. This review presents an in-depth analysis of the mechanisms driving cancer initiation, focusing on roles carcinogenic chemicals, anticancer therapies, chemo-preventive agents. The discussion encompasses broad spectrum carcinogens: chemical agents like polycyclic aromatic hydrocarbons, physical such as ionizing radiation, biological viruses, certain therapeutic drugs. multistep nature carcinogenesis—comprising promotion, progression phases—is detailed, with emphasis epigenetic alterations. Methods for testing carcinogenicity, in vitro vivo studies epidemiological approaches, are highlighted their significance identifying potential carcinogens understanding mechanisms. To classify regulate exposures, also looks at risk management plans regulatory frameworks used agencies European Chemicals Agency (ECHA), Environmental Protection (EPA), International Research (IARC). Additionally, emerging trends treatment, precision oncology, immunotherapy, early detection technologies, explored, alongside ongoing challenges health disparities ethical issues. emphasizes necessity multidisciplinary approach, involving collaboration among researchers, clinicians, bodies, public organizations, translate scientific findings into effective prevention, detection, treatment strategies.

Language: Английский

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Precision Oncology, Signaling Pathways Reprogramming and Targeted Therapy: A Holistic Approach to Molecular Cancer Therapeutic

Authorea (Authorea), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Cancer is a fatal genetic disease involving unregulated cell growth and proliferation with varying underlying complexities including immune evasion, treatment resistance recurrence, optimized required for proper cure.Molecular studies have revealed that tumors are extremely heterogeneous in nature, leading to the complexity of cancer development, which ultimately linked its machinery.It would require effective targeting dysregulated molecular mechanisms factors, regulatory proteins, adhesion molecules, molecules system mainly driven by alterations tumor suppressor genes oncogenes may vary among different types.Importantly, patients same type respond differently available treatments, indicating need patient-specific options.Thus, in-depth genomic patients' needed fully understand determinants initiation progression targeted therapy.Precision oncology has evolved as form therapy focused on profiling identify involved manifestation tailored individualized disease.Accordingly, there been great developments formulation production anticancer agents recent years owing advances technologies enabling precise oncogenic pathways progression.This article aims briefly explain foundations frontiers precision context advancements tools techniques associated process assess scope importance realizing intended goals.

Language: Английский

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AhR and STAT3: A Dangerous Duo in Chemical Carcinogenesis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2744 - 2744

Published: March 18, 2025

Human chemical carcinogenesis is a multistage process where chemicals or their metabolites cause irreversible changes in normal cell physiology, eventually leading to uncontrolled proliferation, transforming into cancerous one. Signal transducer and activator of transcription 3 (STAT3) cytoplasmic factor that regulates differentiation, apoptosis, angiogenesis, inflammation, immune responses. Its aberrant activation triggers tumor progression by promoting the expression oncogenic genes; thus, STAT3 classified as an oncoprotein. The aryl hydrocarbon receptor (AhR) ligand-activated responds wide variety chemicals, including carcinogens like dioxins, inducing genes associated with detoxification, regulation. Recent reports show AhR plays critical role cancer development maintenance. may interact signaling pathways, pathway, which mediates carcinogenic effects several pollutants. Various agents, such industrial waste compounds, can alter activity different types cancers. Understanding complex STAT3-AhR network regulation could open new avenues for prevention treatment, particularly personalized medicine, aiming improve life expectancy achieving complete cure.

Language: Английский

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Apigeninidin-enriched Sorghum bicolor (L. Moench) extracts alleviate Aflatoxin B₁-induced dysregulation of male rat hypothalamic-reproductive axis

Experimental Biology and Medicine, Journal Year: 2022, Volume and Issue: 247(15), P. 1301 - 1316

Published: June 6, 2022

We examined the protective effect of apigeninidin (API)-enriched fraction from Sorghum bicolor sheaths extracts (SBE-05, SBE-06, and SBE-07) against aflatoxin B1 (AFB1)-induced dysregulation male rat's reproductive system that may trigger infertility. Male rats (160 ± 12 g) were treated with AFB1 (50 µg/kg) along 5 or 10 mg/kg SBE-05, SBE-07 for 28 days. Subsequently, we assessed hormone-prolactin, FSH, LH, testosterone levels, testicular function enzymes. Moreover, rats' testes, epididymis, hypothalamus oxidative inflammatory stress biomarkers, caspase-9 activity tissues pathology. observed comparative to alone rats, API co-treatment significantly (p < 0.05) abated AFB1-mediated decrease in prolactin antioxidant defenses lessened lipid peroxidation (LPO) reactive oxygen nitrogen species levels organs-testes, hypothalamus. AFB1-induced hormone decreases-testosterone, LH; caused improvement sperm quantity quality. increase pro-inflammatory cytokine, increased interleukin-10 level, an anti-inflammatory cytokine reduced activities. In addition, alterations tissue histology. Our findings suggest S. API-enrich have active antioxidative, antiapoptotic, activities, which can protect dysfunction hypothalamic-pituitary-gonadal axis.

Language: Английский

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Toxic heavy metal ions contamination in the aqueous environment, its toxicity and methods of microbial remediation

Green Chemistry Letters and Reviews, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 6, 2024

Heavy metal compounds are used in a variety of industrial processes, including tanning, chrome plating, anti-corrosion treatments, and wood preservation. ion pollution water wastewater is often caused by effluent discharge into open sources. Toxic heavy ions such as As (III), Cr (VI), Cd (II), Pb (II) well-known enter the body through pathways, food chain, respiration, skin absorption, drinking water. These produce oxidative stress cells, resulting cell organelle destruction. metals toxicity may cause genetic material mutation or change, histone modification, epigenetic alteration at various stages. Furthermore, linked to heart failure, renal damage, liver problems. For cleanup, several standard approaches utilized. Nonetheless, these technologies costly result toxic sludge after treatment. result, there an urgent need for appropriate, environmentally safe, efficient removal technology. removal, microbial-based regarded both benign cost-effective. This review focuses on water, its harmful consequences, cleanup microbiological means.

Language: Английский

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Exploring the Role of Clustered Mutations in Carcinogenesis and Their Potential Clinical Implications in Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6744 - 6744

Published: June 19, 2024

Abnormal cell proliferation and growth leading to cancer primarily result from cumulative genome mutations. Single gene mutations alone do not fully explain onset progression; instead, clustered mutations—simultaneous occurrences of multiple mutations—are considered be pivotal in development advancement. These can affect different genes pathways, resulting cells undergoing malignant transformation with functional abnormalities. Clustered influence rates, metastatic potential, drug treatment sensitivity. This summary highlights the various types characteristics understand their associations carcinogenesis discusses potential clinical significance cancer. As a unique mutation type, may involve genomic instability, DNA repair mechanism defects, environmental exposures, potentially correlating responsiveness immunotherapy. Understanding underlying processes enhances our comprehension progression, providing new diagnostic therapeutic approaches for

Language: Английский

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Anticancer potential of phytochemicals derived from mangrove plants: Comprehensive mechanistic insights

Food Science & Nutrition, Journal Year: 2024, Volume and Issue: 12(9), P. 6174 - 6205

Published: July 10, 2024

Abstract Cancer is a collection of illnesses characterized by aberrant cellular proliferation that can infiltrate or metastasize to distant anatomical sites, posing notable threat human well‐being due its substantial morbidity and death rates worldwide. The potential plant‐derived natural compounds as anticancer medicines has been assessed owing their favorable attributes few side effects significant antitumor activity. Mangrove plants derived have scientifically shown exhibit many beneficial biological activities, such anti‐inflammatory, immunomodulatory, antioxidant, neuroprotective, cardioprotective, hepatoprotective properties. This study summarized mangrove agents, with an emphasis on the underlying molecular mechanisms. To explore this, we gathered data preclinical (in vivo in vitro) from reputable literature spanning 2000 2023. We conducted thorough searches various academic databases, including PubMed, ScienceDirect, Wiley Online, SpringerLink, Google Scholar, Scopus, Web Science. results demonstrated promising properties pharmacological test systems through mechanisms, induction oxidative stress mitochondrial dysfunction, cytotoxicity, genotoxicity, cell cycle arrest, apoptosis, autophagy, antiproliferative, antimetastatic, other miscellaneous actions. Upon observation pertinent information, it suggested chemicals may serve lead development novel drugs for cancer therapy.

Language: Английский

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Therapeutic Strategies to Enhance Tumor Antigenicity: Making the Tumor Detectable by the Immune System

Biomedicines, Journal Year: 2022, Volume and Issue: 10(8), P. 1842 - 1842

Published: July 30, 2022

Cancer immunotherapy has revolutionized the oncology field, but many patients still do not respond to current approaches. One of main challenges in broadening range responses this type treatment is limited source tumor neoantigens. T cells constitute a line defense against cancer, and decisive step trigger their activation mediated by antigen recognition. Antigens allow immune system differentiate between self foreign, which constitutes critical recognition cancer consequent development or control malignancy. keystones achieving successful antitumor response presence potent antigens, known as However, tumors develop strategies evade resist immunotherapies, present low mutation burden limiting antigenicity. Therefore, new approaches must be taken into consideration overcome these shortcomings. The possibility making more antigenic represents promising front further improve success cancer. Throughout review, we explored different state-of-the-art tools induce presentation antigens intervening at protein, mRNA genomic levels malignant cells.

Language: Английский

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