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Cancer remains a major global health burden, with rising incidence and mortality linked to aging populations and increased exposure to genotoxic agents. Oxidative stress plays a critical role in cancer development, progression, and resistance to therapy. The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1)-antioxidant response element (ARE) signaling pathway is central to maintaining redox balance by regulating the expression of antioxidant and detoxification genes. Under physiological conditions, this pathway protects cells from oxidative damage, however, sustained activation of NRF2 in cancer, often due to mutations in KEAP1, supports tumor cell survival, drug resistance, and metabolic reprogramming. Recent studies demonstrate that NRF2 enhances glutathione (GSH) synthesis, induces detoxifying enzymes, and upregulates drug efflux transporters, collectively contributing to resistance against chemotherapy and targeted therapies. The inhibition of NRF2 using small molecules or dietary phytochemicals has shown promise in restoring drug sensitivity in preclinical cancer models. This review highlights the dual role of NRF2 in redox regulation and cancer therapy, emphasizing its potential as a therapeutic target. While targeting NRF2 offers a novel approach to overcoming treatment resistance, further research is needed to enhance specificity and facilitate clinical translation. Show less

Non‑small cell lung cancer (NSCLC) is one of the most prevalent and lethal types of cancers worldwide and its high incidence and mortality rates pose a significant public health challenge. Despite significant advances in targeted therapy and immunotherapy, the overall prognosis of patients with NSCLC remains poor. Hypoxia is a critical driving factor in tumor progression, influencing the biological behavior of tumor cells through complex molecular mechanisms. The present review systematically examined the role of the hypoxic microenvironment in NSCLC, demonstrating its crucial role in promoting tumor cell growth, invasion and metastasis. Additionally, it has been previously reported that the hypoxic microenvironment enhances tumor cell resistance by activating hypoxia‑inducible factor and regulating exosome secretion. The hypoxic microenvironment also enables tumor cells to adapt to low oxygen and nutrient‑deficient conditions by enhancing metabolic reprogramming, such as through upregulating glycolysis. Further studies have shown that the hypoxic microenvironment facilitates immune escape by modulating tumor‑associated immune cells and suppressing the antitumor response of the immune system. Moreover, the hypoxic microenvironment increases tumor resistance to radiotherapy, chemotherapy and other types of targeted therapy through various pathways, significantly reducing the therapeutic efficacy of these treatments. Therefore, it could be suggested that early detection of cellular hypoxia and targeted therapy based on hypoxia may offer new therapeutic approaches for patients with NSCLC. The present review not only deepened the current understanding of the mechanisms of action and role of the hypoxic microenvironment in NSCLC but also provided a solid theoretical basis for the future development of precision treatments for patients with NSCLC. Show less

Ferroptosis is a regulated form of cell death characterized by iron-dependent lipid peroxidation. It plays a crucial role in various pathological conditions, including neurodegenerative diseases, cancer, ischemia–reperfusion injury, and organ failure. This review systematically explores the key mechanisms underlying ferroptosis, including polyunsaturated fatty acidcontaining phospholipid (PUFA-PL) peroxidation, iron metabolism, and mitochondrial dysfunction. Additionally, we summarize major endogenous ferroptosis defense systems, including the SLC7A11-glutathione (GSH)-glutathione peroxidase Show less

Introduction Mitochondria are essential organelles for many aspects of cellular homeostasis. They play an indispensable role in the development and progression of diseases, particularly cancer which is a major cause of death worldwide. We analyzed the scientific research output on mitochondria and cancer via PubMed and Web of Science over the period 1990–2023. Methods Bibliometric analysis was performed by extracting data linking mitochondria to cancer pathogenesis over the period 1990–2023 from the PubMed database which has a precise and specific search engine. Only articles and reviews were considered. Since PubMed does not support analyses by countries or institutions, we utilized InCites, an analytical tool developed and marketed by Clarivate Analytics. We also used the VOSviewer software developed by the Centre for Science and Technology Studies (Bibliometric Department of Leiden University, Leiden, Netherlands), which enables us to graphically represent links between countries, authors or keywords in cluster form. Finally, we used iCite, a tool developed by the NIH (USA) to access a dashboard of bibliometrics for papers associated with a portfolio. This module can therefore be used to measure whether the research carried out is still basic, translational or clinical. Results In total, 169,555 publications were identified in PubMed relating to ‘mitochondria’, of which 34,949 (20.61%) concerned ‘mitochondria’ and ‘dysfunction’ and 22,406 (13.21%) regarded ‘mitochondria’ and ‘cancer’. Hence, not all mitochondrial dysfunctions may lead to cancer or enhance its progression. Qualitatively, the disciplines of journals were classified into 166 categories among which cancer specialty accounts for only 4.7% of publications. Quantitatively, our analysis showed that cancer/neoplasms in the liver (2569 articles) were placed in the first position. USA occupied the first position among countries contributing the highest number of publications (5695 articles), whereas Egypt came in the thirty-eight position with 84 publications (0.46%). Importantly, USA is the first-ranked country having both the top 1% and 10% impact indicators with 207 and 1459 articles, respectively. By crossing the query ‘liver neoplasms’ (155,678) with the query ‘mitochondria’ (169,555), we identified 1336 articles in PubMed over the study period. Among these publications, research areas were classified into 65 categories with the highest percentage of documents included in biochemistry and molecular biology (28.92%), followed by oncology (23.31%). Conclusions This study underscores the crucial yet underrepresented role of mitochondria in cancer research. Despite their significance in cancer pathogenesis, the proportion of related publications remains relatively low. Our findings Supplementary Information The online version contains supplementary material available at https://​doi.​org/​10.​1007/​s12672-​025-​ 02139-5. * Abeer El Wakil, abeer_elwakil@alexu.edu.eg; Patrick Devos, patrick.devos@univ-lille.fr; Heba Abdelmegeed, hn.abdelmegeed@ nrc.sci.eg; Alaa Kamel, alaa.kamel_pg@alexu.edu.eg | 1Department of Biological and Geological Sciences, Faculty of Education, Alexandria University, Alexandria 21526, Egypt. 2Université Lille, Lillometrics, 59000 Lille, France. 3CHU Lille, Direction de la Recherche et de l’Innovation, 59000 Lille, France. 4Department of Chemistry of Natural Compounds, National Research Centre, Giza, Egypt. 5Department of Zoology, Faulty of Science, Alexandria University, Alexandria, Egypt. Discover Oncology (2025) 16:517 | https://doi.org/10.1007/s12672-025-02139-5 Vol.:(0123456789) Research Discover Oncology (2025) 16:517 | https://doi.org/10.1007/s12672-025-02139-5 highlight the need for further research to deepen our understanding of mitochondrial mechanisms in cancer, which could pave the way for new therapeutic strategies. Graphical Abstract Show less

Mitochondria are the energy production centers in cells and have unique genetic information. Due to the irreplaceable function of mitochondria, mitochondrial dysfunction often leads to pathological changes. Mitochondrial dysfunction induces an imbalance between oxidation and antioxidation, mitochondrial DNA (mtDNA) damage, mitochondrial dynamics dysregulation, and changes in mitophagy. It results in oxidative stress due to excessive reactive oxygen species (ROS) generation, which contributes to cell damage and death. Mitochondrial dysfunction can also trigger inflammation through the activation of damage-associated molecular patterns (DAMPs), inflammasomes and inflammatory cells. Besides, mitochondrial alterations in the functional regulation, energy metabolism and genetic stability accompany the aging process, and there has been a lot of evidence suggesting that oxidative stress and inflammation, both of which are associated with mitochondrial dysfunction, are predisposing factors of aging. Therefore, this review hypothesizes that mitochondria serve as central hubs regulating oxidative stress, inflammation, and aging, and their dysfunction contributes to various diseases, including cancers, cardiovascular diseases, neurodegenerative disorders, metabolic diseases, sepsis, ocular pathologies, liver diseases, and autoimmune conditions. Moreover, we outline therapies aimed at various mitochondrial dysfunctions, highlighting their performance in animal models and human trials. Additionally, we focus on the limitations of mitochondrial therapy in clinical applications, and discuss potential future research directions for mitochondrial therapy. Show less

The nucleolus, a membraneless organelle crucial for ribosome production, has a unique nanoscale structure whose organization is responsive to cell signals and disease progression. Here, we highlight the potential of Expansion Microscopy (ExM) for capturing intricate spatial and functional information about membraneless organelles such as the nucleolus and nuclear foci. We apply dual protein Expansion Microscopy (dual-proExM) in combination with click Expansion Microscopy (click-ExM) to capture images at the highest resolution reported for the nucleolus of ∼45 ± 2 nm. Inhibition of nucleolar processes triggers a nucleolar stress response, causing distinct structural rearrangements whose molecular basis is an area of active investigation. We investigate time-dependent changes in nucleolar structure and function under nucleolar stress induced by oxaliplatin, actinomycin D, and other platinum-based compounds. Our findings reveal new stages that occur prior to the complete sequestration of RNA Pol I into nucleolar caps, shedding light on the early mechanisms of the nucleolar stress response. RNA transcription is linked to nanoscale protein rearrangements using a combination of click-ExM and pro-ExM, revealing locations of active transcripts during the early stages of nucleolar stress reorganization. With prolonged stress, fibrillarin and NPM1 segregate from the nucleolus into nucleoplasmic foci that are for the first time imaged at nanometer resolution. In addition to revealing new morphological information about the nucleolus, this study demonstrates the potential of ExM for imaging membraneless organelles with nanometer-scale precision. Show less

Chemotherapy for cancer frequently uses platinum-based medications, including oxaliplatin, carboplatin, and cisplatin; however, due to their high systemic toxicity, lack of selectivity, drug resistance, and other side effects, platinum-based medications have very limited clinical application. As a first-line medication in antitumor therapy, oxaliplatin must be administered to minimize side effects while achieving anticancer objectives. A new CDC7 inhibitor called XL413 has demonstrated promising antitumor therapeutic effects in a variety of malignant tumors and may have anticancer properties. This offers a fresh viewpoint on how to lessen oxaliplatin resistance and, specifically, increase the potency of already prescribed anticancer therapies. In this paper, the current developments in anticancer therapy are discussed, along with the many mechanisms of oxaliplatin's antitumor effects, clinical treatment challenges, and related approaches. We conducted more research on oxaliplatin resistance that arose during chemotherapy and searched for ways to lessen it in order to enhance its chemotherapeutic performance. Ultimately, we studied how distinct resistance routes relate to one another. Meanwhile, XL413, a novel CDC7 inhibitor, offers a perspective on the possibilities for developing treatment approaches for this innovation point. The search terms "Oxaliplatin, XL413, drug resistance, cancer treatment," etc., were applied in the X-MOL and PubMed databases for this review's literature search. Boolean logic was then employed to maximize the search approach. These databases can offer thorough research data and cover a broad range of biological publications. Excluded publications were works of low relevance, duplicates, or those with insufficient information. The mechanism of oxaliplatin's anticancer effect, oxaliplatin resistance and its amelioration, and the role of XL413 in oxaliplatin treatment were the main topics of the 140 publications that were ultimately included for analysis. Show less

High-Grade Serous Ovarian Cancer (HGSOC) is the most common and lethal subtype of ovarian cancer, known for its high aggressiveness and extensive genomic alterations. Typically diagnosed at an advanced stage, HGSOC presents formidable challenges in drug therapy. The limited efficacy of standard treatments, development of chemoresistance, scarcity of targeted therapies, and significant tumor heterogeneity render this disease incurable with current treatment options, highlighting the urgent need for novel therapeutic approaches to improve patient outcomes. In this study we report a straightforward and stereoselective synthetic route to novel Pd(II)-vinyl and -butadienyl complexes bearing a wide range of monodentate and bidentate ligands. Most of the synthesized complexes exhibited good to excellent in vitro anticancer activity against ovarian cancer cells. Particularly promising is the water-soluble complex bearing two PTA (1,3,5-triaza-7-phosphaadamantane) ligands and the Pd(II)-butadienyl fragment. This compound combines excellent cytotoxicity towards cancer cells with substantial inactivity towards non-cancerous ones. This derivative was selected for further studies on ex vivo tumor organoids and in vivo mouse models, which demonstrate its remarkable efficacy with surprisingly low collateral toxicity even at high dosages. Moreover, this class of compounds appears to operate through a ferroptotic mechanism, thus representing the first such example for an organopalladium compound. Show less

Ferroptosis, the non-apoptotic, iron-dependent form of cell death is an unavoidable outcome and byproduct of cellular metabolism. Reactive oxygen species generation during metabolic activities transcends to ­Fe2+-induced lipid peroxidation, leading to ferroptosis. Cancer cells being highly metabolic are more prone to ferroptosis. However, their neoplastic nature enables them to bypass ferroptosis and become ferroptosis-resistant. The capability of cancer cells to reprogram its metabolic activities is one of its finest abilities to abort oxidative damage, and hence ferroptosis. Moreover, the reprogrammed metabolism of cancer cells, also associates with the radical trapping antioxidant Show less

Claudin (CLDN) proteins are extensively studied due to their critical role in maintaining tissue barriers and cell polarity. However, significant gaps remain in understanding the functional mechanisms of their sequence motifs and the molecular mechanisms of their interactions with other tight junction proteins. This review systematically examines the multifunctional properties of the CLDN protein family from the perspectives of sequence and structure. During evolution, CLDN family members have developed highly conserved structural features, particularly key conserved sites within the first Show less

N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic mRNA and has emerged as a pivotal regulator of gene expression at the post-transcriptional level. In the tumor immune microenvironment, tumor-associated macrophages (TAMs) represent a highly plastic and heterogeneous population that profoundly influences cancer progression, immune evasion, and therapeutic response. Recent studies have uncovered that m6A modification, mediated by dynamic “writers,” “erasers,” and “readers,” exerts critical regulatory effects on TAM differentiation, polarization, and functional reprogramming. By modulating the stability, translation, and decay of transcripts involved in inflammatory signaling, metabolic adaptation, and immune checkpoints, m6A shapes the balance between tumor-promoting (M2-like) and tumor-suppressive (M1-like) macrophage phenotypes. Moreover, dysregulation of m6A machinery in TAMs has been linked to the suppression of anti-tumor immunity and resistance to immunotherapy, highlighting its translational potential as a therapeutic target. This review summarizes current advances in understanding the roles and mechanisms of m6A modification in TAM biology, discusses its implications in tumor immunity, and outlines the challenges and opportunities of targeting the m6A–TAM axis for cancer treatment. Show less

N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic mRNA and has emerged as a pivotal regulator of gene expression at the post-transcriptional level. In the tumor immune microenvironment, tumor-associated macrophages (TAMs) represent a highly plastic and heterogeneous population that profoundly influences cancer progression, immune evasion, and therapeutic response. Recent studies have uncovered that m6A modification, mediated by dynamic “writers,” “erasers,” and “readers,” exerts critical regulatory effects on TAM differentiation, polarization, and functional reprogramming. By modulating the stability, translation, and decay of transcripts involved in inflammatory signaling, metabolic adaptation, and immune checkpoints, m6A shapes the balance between tumor-promoting (M2-like) and tumor-suppressive (M1-like) macrophage phenotypes. Moreover, dysregulation of m6A machinery in TAMs has been linked to the suppression of anti-tumor immunity and resistance to immunotherapy, highlighting its translational potential as a therapeutic target. This review summarizes current advances in understanding the roles and mechanisms of m6A modification in TAM biology, discusses its implications in tumor immunity, and outlines the challenges and opportunities of targeting the m6A–TAM axis for cancer treatment. Show less

Academic Editor: Sabrina Venditti Received: 22 May 2025 Revised: 5 July 2025 N6-methyladenosine (m6A) represents the most common and thoroughly investigated RNA modification and exerts essential functions in regulating gene expression through influencing the RNA stability, the translation efficiency, alternative splicing, and nuclear export processes. The rapid development of high-throughput sequencing approaches, including miCLIP and MeRIP-seq, has profoundly transformed epitranscriptomics research. Show less

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, Show less

Nucleophosmin (NPM1) is a key nucleolar protein released from the nucleolus in response to stress stimuli. NPM1 functions as a stress regulator with nucleic acid and protein chaperone activities, rapidly shuttling between the nucleus and cytoplasm. NPM1 is ubiquitously expressed in tissues and can be found in the nucleolus, nucleoplasm, cytoplasm, and extracellular environment. It plays a central role in various biological processes such as ribosome biogenesis, cell cycle regulation, cell proliferation, DNA damage repair, and apoptosis. In addition, it is highly expressed in cancer cells and solid tumors, and its mutation is a major cause of acute myeloid leukemia (AML). This review focuses on NPM1's structural features, functional diversity, subcellular distribution, and role in stress modulation. Show less

DNA adducting drugs, including alkylating agents and platinum-containing drugs, are prominent in cancer chemotherapy. Their mechanisms of action involve direct interaction with DNA, resulting in the formation of DNA addition products known as DNA adducts. While these adducts are well-accepted to induce cancer cell death, understanding of their specific chemotypes and their role in drug therapy response remain limited. This perspective aims to address this gap by investigating the metabolic activation and chemical characterization of DNA adducts formed by the U.S. FDA-approved drugs. Moreover, clinical studies on DNA adducts as potential biomarkers for predicting patient responses to drug efficacy are examined. The overarching goal is to engage the interest of medicinal chemists and stimulate further research into the use of DNA adducts as biomarkers for guiding personalized cancer treatment. Show less

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

Although 5-fluorouracil (5-FU) is the primary chemotherapy treatment for colorectal cancer (CRC), its efficacy is limited by drug resistance. Ferroptosis activation is a promising treatment for 5-FU-resistant cancer cells; however, potential therapeutic targets remain elusive. This study investigated ferroptosis vulnerability and dihydroorotate dehydrogenase (DHODH) activity using stable, 5-FU-resistant CRC cell lines and xenograft models. Ferroptosis was characterized by measuring malondialdehyde levels, assessing lipid metabolism and peroxidation, and using mitochondrial imaging and assays. DHODH function is investigated through gene knockdown experiments, tumor behavior assays, mitochondrial import reactions, intramitochondrial localization, enzymatic activity analyses, and metabolomics assessments. Intracellular lipid accumulation and mitochondrial DHODH deficiency led to lipid peroxidation overload, weakening the defense system of 5-FU-resistant CRC cells against ferroptosis. DHODH, primarily located within the inner mitochondrial membrane, played a crucial role in driving intracellular pyrimidine biosynthesis and was redistributed to the cytosol in 5-FU-resistant CRC cells. Cytosolic DHODH, like its mitochondrial counterpart, exhibited dihydroorotate catalytic activity and participated in pyrimidine biosynthesis. This amplified intracellular pyrimidine pools, thereby impeding the efficacy of 5-FU treatment through molecular competition. These findings contribute to the understanding of 5-FU resistance mechanisms and suggest that ferroptosis and DHODH are promising therapeutic targets for patients with CRC exhibiting resistance to 5-FU. Show less

Programmed cell death (PCD) is a fundamental biological process for maintaining cellular equilibrium and regulating development, health, and disease across all living organisms. Among the various types of PCD, apoptosis plays a pivotal role in numerous diseases, notably cancer. Cancer cells frequently develop mechanisms to evade apoptosis, increasing resistance to standard chemotherapy treatments. This resistance has prompted extensive research into alternative mechanisms of programmed cell death. One such pathway is oncosis, characterized by significant energy consumption, cell swelling, dilation of the endoplasmic reticulum, mitochondrial swelling, and nuclear chromatin aggregation. Recent research suggests that oncosis can impact conditions such as chemotherapeutic cardiotoxicity, myocardial ischemic injury, stroke, and cancer, mediated by specific oncosis-related proteins. In this review, we provide a detailed examination of the morphological and molecular features of oncosis and discuss various natural or small molecule compounds that can induce this type of cell death. Additionally, we summarize the current understanding of the molecular mechanisms underlying oncosis and its role in both normal physiology and pathological conditions. These insights aim to illuminate future research directions and propose innovative strategies for leveraging oncosis as a therapeutic tool against human diseases and cancer resistance. Show less

Ferroptosis, a regulated form of cell death, is intricately linked to iron‑dependent lipid peroxidation. Recent evidence strongly supports the induction of ferroptosis as a promising strategy for treating cancers resistant to conventional therapies. A key player in ferroptosis regulation is ferroptosis suppressor protein 1 (FSP1), which promotes cancer cell resistance by promoting the production of the antioxidant form of coenzyme Q10. Of note, FSP1 confers resistance to ferroptosis independently of the glutathione (GSH) and glutathione peroxidase‑4 pathway. Therefore, targeting FSP1 to weaken its inhibition of ferroptosis may be a viable strategy for treating refractory cancer. This review aims to clarify the molecular mechanisms underlying ferroptosis, the specific pathway by which FSP1 suppresses ferroptosis and the effect of FSP1 inhibitors on cancer cells. Show less

Oxidation-reduction (redox) reactions are central to the existence of life. Reactive species of oxygen, nitrogen and sulfur mediate redox control of a wide range of essential cellular processes. Yet, excessive levels of oxidants are associated with ageing and many diseases, including cardiological and neurodegenerative diseases, and cancer. Hence, maintaining the fine-tuned steady-state balance of reactive species production and removal is essential. Here, we discuss new insights into the dynamic maintenance of redox homeostasis (that is, redox homeodynamics) and the principles underlying biological redox organization, termed the 'redox code'. We survey how redox changes result in stress responses by hormesis mechanisms, and how the lifelong cumulative exposure to environmental agents, termed the 'exposome', is communicated to cells through redox signals. Better understanding of the molecular and cellular basis of redox biology will guide novel redox medicine approaches aimed at preventing and treating diseases associated with disturbed redox regulation. Show less

A nanoscale polymer layer formed by mucins at the surface of tumour cells protects them against immune cell attack. This shield can be circumvented through immune cell engineering, using chimeric antigen receptors to stimulate natural killer and T cells or by tethering glycocalyx-editing enzymes to immune cells. Show less

The Keap1-Nrf2 signaling pathway plays a crucial role in cellular defense against oxidative stress-induced damage. Its activation entails the expression and transcriptional regulation of several proteins involved in detoxification and antioxidation processes within the organism. Keap1, serving as a pivotal transcriptional regulator within this pathway, exerts control over the activity of Nrf2. Various post-translational modifications (PTMs) of Keap1, such as alkylation, glycosylation, glutathiylation, S-sulfhydration, and other modifications, impact the binding affinity between Keap1 and Nrf2. Consequently, this leads to the accumulation of Nrf2 and its translocation to the nucleus, and subsequent activation of downstream antioxidant genes. Given the association between the Keap1-Nrf2 signaling pathway and various diseases such as cancer, neurodegenerative disorders, and diabetes, comprehending the post-translational modification of Keap1 not only deepens our understanding of Nrf2 signaling regulation but also contributes to the identification of novel drug targets and biomarkers. Consequently, this knowledge holds immense importance in the prevention and treatment of diseases induced by oxidative stress. Show less

Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built with in vitro models that do not match the microenvironmental characteristics of human tissues. Using in vitro models which mimic the physical properties of healthy or cancerous tissues and a physiologically relevant culture medium, we demonstrate that the chemical and physical properties of the microenvironment regulate the composition and topology of the glycocalyx. Remarkably, we find that cancer and age-related changes in the physical properties of the microenvironment are sufficient to adjust immune surveillance via the topology of the glycocalyx, a previously unknown phenomenon observable only with a physiologically relevant culture medium. Show less

Brain cancer is regarded as one of the most life-threatening forms of cancer worldwide. Oxidative stress acts to derange normal brain homeostasis, thus is involved in carcinogenesis in brain. The Nrf2/Keap1/ARE pathway is an important signaling cascade responsible for the maintenance of redox homeostasis, and regulation of antiinflammatory and anticancer activities by multiple downstream pathways. Interestingly, Nrf2 plays a somewhat, contradictory role in cancers, including brain cancer. Nrf2 has traditionally been regarded as a tumor suppressor Show less

Brain cancer is regarded as one of the most life-threatening forms of cancer worldwide. Oxidative stress acts to derange normal brain homeostasis, thus is involved in carcinogenesis in brain. The Nrf2/Keap1/ARE pathway is an important signaling cascade responsible for the maintenance of redox homeostasis, and regulation of antiinflammatory and anticancer activities by multiple downstream pathways. Interestingly, Nrf2 plays a somewhat, contradictory role in cancers, including brain cancer. Nrf2 has traditionally been regarded as a tumor suppressor Show less

PandaOmics is a cloud-based software platform that applies artificial intelligence and bioinformatics techniques to multimodal omics and biomedical text data for therapeutic target and biomarker discovery. PandaOmics generates novel and repurposed therapeutic target and biomarker hypotheses with the desired properties and is available through licensing or collaboration. Targets and biomarkers generated by the platform were previously validated in both in vitro and in vivo studies. PandaOmics is a core component of Insilico Medicine's Pharma.ai drug discovery suite, which also includes Chemistry42 for the de novo generation of novel small molecules, and inClinico─a data-driven multimodal platform that forecasts a clinical trial's probability of successful transition from phase 2 to phase 3. In this paper, we demonstrate how the PandaOmics platform can efficiently identify novel molecular targets and biomarkers for various diseases. Show less

BackgroundAntioxidant supplements are widely used during cancer treatment to prevent oxidative stress, reduce treatment toxicities, and improve patient outcomes. However, current literature reveals significant gaps suggesting that antioxidants may protect both healthy and tumor cells from oxidative damage, thereby reducing treatment efficacy. It is for this reason that antioxidant supplements have become a source of therapeutic controversy.ObjectiveTo review therapeutic controversies over the use of antioxidant supplements during cancer treatment.MethodsScoping review of the international published articles following the Arksey and O’Malley framework, cross-sectional studies, clinical and pre-clinical studies, systematic and umbrella reviews and grey literatures published from 2014 to 2024 with all age patient populations were included. A structured literature search was conducted of CINAHL, EMBASE, MEDLINE, Google Scholar, using key medical subject heading words and Cochrane Collaboration and Joanna Briggs Institute databases. All included studies were reviewed independently by two investigators. Data were extracted, collated by type of antioxidants, summarized in tables and synthesized for analysis.ResultA total of 1, 550 articles were identified. After reviewing all literatures, twenty-one (21) were full-text articles, grey literatures (2), and systematic reviews (42) and umbrella reviews (3), met the criteria for inclusion. In this review, the use of antioxidant supplements can benefit cancer cells in the same way as they do for normal cells during cancer treatment. In addition, not all antioxidants were effective in inhibiting oxidative stress, reduce treatment toxicities, and improve patient outcomes.Conclusion and recommendationsAccording to this review, the use of antioxidant supplements can benefit tumor cells in the same manner as they do for normal cells. Therefore, oncologists should advise not to take antioxidant supplements during chemotherapy and/or radiotherapy. Future research including potential clinical and preclinical trials, mechanistic studies, and exploration of different vitamin and mineral supplement studies are required to uncover the complete potential of antioxidant supplements for cancer treatment or determine their safety and effectiveness when used alongside standard cancer treatments. Furthermore, the results of this review could be used for future systematic review of therapeutic controversies over use of antioxidant supplements during cancer treatment. Show less