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18 pages, 2279 KiB  
Article
MvAl-MFP: A Multi-Label Classification Method on the Functions of Peptides with Multi-View Active Learning
by Yuxuan Peng, Jicong Duan, Yuanyuan Dan and Hualong Yu
Curr. Issues Mol. Biol. 2025, 47(8), 628; https://doi.org/10.3390/cimb47080628 (registering DOI) - 6 Aug 2025
Abstract
The rapid expansion of peptide libraries and the increasing functional diversity of peptides have highlighted the significance of predicting the multifunctional properties of peptides in bioinformatics research. Although supervised learning methods have made advancements, they typically necessitate substantial amounts of labeled data for [...] Read more.
The rapid expansion of peptide libraries and the increasing functional diversity of peptides have highlighted the significance of predicting the multifunctional properties of peptides in bioinformatics research. Although supervised learning methods have made advancements, they typically necessitate substantial amounts of labeled data for yielding accurate prediction. This study presents MvAl-MFP, a multi-label active learning approach that incorporates multiple feature views of peptides. This method takes advantage of the natural properties of multi-view representation for amino acid sequences, meets the requirement of the query-by-committee (QBC) active learning paradigm, and further significantly diminishes the requirement for labeled samples while training high-performing models. First, MvAl-MFP generates nine distinct feature views for a few labeled peptide amino acid sequences by considering various peptide characteristics, including amino acid composition, physicochemical properties, evolutionary information, etc. Then, on each independent view, a multi-label classifier is trained based on the labeled samples. Next, a QBC strategy based on the average entropy of predictions across all trained classifiers is adopted to select a specific number of most valuable unlabeled samples to submit them to human experts for labeling by wet-lab experiments. Finally, the aforementioned procedure is iteratively conducted with a constantly expanding labeled set and updating classifiers until it meets the default stopping criterion. The experiments are conducted on a dataset of multifunctional therapeutic peptides annotated with eight functional labels, including anti-bacterial properties, anti-inflammatory properties, anti-cancer properties, etc. The results clearly demonstrate the superiority of the proposed MvAl-MFP method, as it can rapidly improve prediction performance while only labeling a small number of samples. It provides an effective tool for more precise multifunctional peptide prediction while lowering the cost of wet-lab experiments. Full article
(This article belongs to the Special Issue Challenges and Advances in Bioinformatics and Computational Biology)
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28 pages, 845 KiB  
Review
Circulating Tumor DNA in Prostate Cancer: A Dual Perspective on Early Detection and Advanced Disease Management
by Stepan A. Kopytov, Guzel R. Sagitova, Dmitry Y. Guschin, Vera S. Egorova, Andrei V. Zvyagin and Alexey S. Rzhevskiy
Cancers 2025, 17(15), 2589; https://doi.org/10.3390/cancers17152589 - 6 Aug 2025
Abstract
Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor [...] Read more.
Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article
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19 pages, 1628 KiB  
Review
The Role of Non-Coding RNAs in the Regulation of Oncogenic Pathways in Breast and Gynaecological Cancers
by Ammar Ansari, Aleksandra Szczesnowska, Natalia Haddad, Ahmed Elbediwy and Nadine Wehida
Non-Coding RNA 2025, 11(4), 61; https://doi.org/10.3390/ncrna11040061 - 6 Aug 2025
Abstract
Female cancers such as breast and gynaecological cancers contribute to a significant global health burden and are a leading cause of fatality among women. With current treatment options often limited by resistance to cytotoxic drugs, side effects and lack of specificity to the [...] Read more.
Female cancers such as breast and gynaecological cancers contribute to a significant global health burden and are a leading cause of fatality among women. With current treatment options often limited by resistance to cytotoxic drugs, side effects and lack of specificity to the cancer, there is a pressing need for alternative treatments. Recent research has highlighted the promising role of non-coding RNAs (ncRNA) in regulating these issues and providing more targeted approaches to suppressing key cancer pathways. This review explores the involvement of the various types of non-coding RNAs in regulating key oncogenic pathways, namely, the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin and p53 pathways, in a range of female cancers such as breast, cervical, ovarian and endometrial cancers. Evidence from a multitude of studies suggests that non-coding RNAs function as double-edged swords, serving as both oncogenes and tumour suppressors, depending on their expression and cellular interactions. By mapping and investigating these regulatory interactions, this review demonstrates the complexity and dual functionality of ncRNAs in cancer. Understanding these complex mechanisms is essential for the development of new and effective ncRNA-based diagnostic methods and targeted therapies in female cancer treatment. Full article
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30 pages, 2414 KiB  
Review
Melittin-Based Nanoparticles for Cancer Therapy: Mechanisms, Applications, and Future Perspectives
by Joe Rizkallah, Nicole Charbel, Abdallah Yassine, Amal El Masri, Chris Raffoul, Omar El Sardouk, Malak Ghezzawi, Therese Abou Nasr and Firas Kreidieh
Pharmaceutics 2025, 17(8), 1019; https://doi.org/10.3390/pharmaceutics17081019 - 6 Aug 2025
Abstract
Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt [...] Read more.
Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt and NF-κB signaling pathways, and by inducing mitochondrial apoptosis through reactive oxygen species generation and cytochrome c release. However, its clinical application is hindered by its systemic and hemolytic toxicity, rapid degradation in plasma, poor pharmacokinetics, and immunogenicity, necessitating the development of targeted delivery strategies to enable safe and effective treatment. Nanoparticle-based delivery systems have emerged as a promising strategy for overcoming these challenges, offering improved tumor targeting, reduced off-target effects, and enhanced stability. This review provides a comprehensive overview of the mechanisms through which melittin exerts its anticancer effects and evaluates the development of various melittin-loaded nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, micelles, and inorganic systems. It also summarizes the preclinical evidence for melittin nanotherapy across a wide range of cancer types, highlighting both its cytotoxic and immunomodulatory effects. The potential of melittin nanoparticles to overcome multidrug resistance and synergize with chemotherapy, immunotherapy, photothermal therapy, and radiotherapy is discussed. Despite promising in vitro and in vivo findings, its clinical translation remains limited. Key barriers include toxicity, manufacturing scalability, regulatory approval, and the need for more extensive in vivo validation. A key future direction is the application of computational tools, such as physiologically based pharmacokinetic modeling and artificial-intelligence-based modeling, to streamline development and guide its clinical translation. Addressing these challenges through focused research and interdisciplinary collaboration will be essential to realizing the full therapeutic potential of melittin-based nanomedicines in oncology. Overall, this review synthesizes the findings from over 100 peer-reviewed studies published between 2008 and 2025, providing an up-to-date assessment of melittin-based nanomedicine strategies across diverse cancer types. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles, 2nd Edition)
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16 pages, 4092 KiB  
Article
Ribosome Biogenesis Underpins Tumor Progression: A Comprehensive Signature for Survival and Immunotherapy Response Prediction
by Amr R. Elhamamsy, Salma M. Aly, Rajeev S. Samant and Lalita A. Shevde
Cancers 2025, 17(15), 2576; https://doi.org/10.3390/cancers17152576 - 5 Aug 2025
Abstract
Background: RiBi is integral to cell proliferation, and its dysregulation is increasingly recognized as a hallmark of aggressive cancers. We sought to develop and validate a composite “PanRibo-515 score” reflecting RiBi activity across multiple tumor types, assess its prognostic significance, and explore [...] Read more.
Background: RiBi is integral to cell proliferation, and its dysregulation is increasingly recognized as a hallmark of aggressive cancers. We sought to develop and validate a composite “PanRibo-515 score” reflecting RiBi activity across multiple tumor types, assess its prognostic significance, and explore its relationship with immune checkpoint therapy outcomes. Methods: We curated 515 RiBi–associated genes (PanRibo-515) and used a LASSO regression-based strategy on a training dataset (GSE202203) to select the prognostically most relevant subset of 68 genes (OncoRibo-68). Directionality (positive or negative impact on survival) was assigned based on the sign of the LASSO coefficients. We integrated a forward selection approach to identify a refined subset of genes for computing the OncoRibo-68 score. For validation, patients in The Cancer Genome Atlas (TCGA) were stratified into high or low OncoRibo-68 score groups for survival analyses. Additional validation for immunotherapy response was conducted using bioinformatic platforms used for immunotherapy response analysis. Results: A higher OncoRibo-68 score consistently correlated with poorer overall and progression-free survival across multiple cancers. Elevated OncoRibo-68 score was linked to an immunosuppressive tumor microenvironment, but interestingly to increased response to checkpoint inhibitors. Conclusions: Our findings highlight RiBi as an important determinant of tumor aggressiveness and identify the OncoRibo-68 score as a promising biomarker for risk stratification and therapy selection. Future research may evaluate whether targeting RiBi pathways could enhance treatment efficacy, particularly in combination with immunotherapy. Full article
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22 pages, 2630 KiB  
Review
Transfection Technologies for Next-Generation Therapies
by Dinesh Simkhada, Su Hui Catherine Teo, Nandu Deorkar and Mohan C. Vemuri
J. Clin. Med. 2025, 14(15), 5515; https://doi.org/10.3390/jcm14155515 - 5 Aug 2025
Abstract
Background: Transfection is vital for gene therapy, mRNA treatments, CAR-T cell therapy, and regenerative medicine. While viral vectors are effective, non-viral systems like lipid nanoparticles (LNPs) offer safer, more flexible alternatives. This work explores emerging non-viral transfection technologies to improve delivery efficiency [...] Read more.
Background: Transfection is vital for gene therapy, mRNA treatments, CAR-T cell therapy, and regenerative medicine. While viral vectors are effective, non-viral systems like lipid nanoparticles (LNPs) offer safer, more flexible alternatives. This work explores emerging non-viral transfection technologies to improve delivery efficiency and therapeutic outcomes. Methods: This review synthesizes the current literature and recent advancements in non-viral transfection technologies. It focuses on the mechanisms, advantages, and limitations of various delivery systems, including lipid nanoparticles, biodegradable polymers, electroporation, peptide-based carriers, and microfluidic platforms. Comparative analysis was conducted to evaluate their performance in terms of transfection efficiency, cellular uptake, biocompatibility, and potential for clinical translation. Several academic search engines and online resources were utilized for data collection, including Science Direct, PubMed, Google Scholar Scopus, the National Cancer Institute’s online portal, and other reputable online databases. Results: Non-viral systems demonstrated superior performance in delivering mRNA, siRNA, and antisense oligonucleotides, particularly in clinical applications. Biodegradable polymers and peptide-based systems showed promise in enhancing biocompatibility and targeted delivery. Electroporation and microfluidic systems offered precise control over transfection parameters, improving reproducibility and scalability. Collectively, these innovations address key challenges in gene delivery, such as stability, immune response, and cell-type specificity. Conclusions: The continuous evolution of transfection technologies is pivotal for advancing gene and cell-based therapies. Non-viral delivery systems, particularly LNPs and emerging platforms like microfluidics and biodegradable polymers, offer safer and more adaptable alternatives to viral vectors. These innovations are critical for optimizing therapeutic efficacy and enabling personalized medicine, immunotherapy, and regenerative treatments. Future research should focus on integrating these technologies to develop next-generation transfection platforms with enhanced precision and clinical applicability. Full article
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15 pages, 2053 KiB  
Article
Unveiling Radon Concentration in Geothermal Installation: The Role of Indoor Conditions and Human Activity
by Dimitrios-Aristotelis Koumpakis, Savvas Petridis, Apostolos Tsakirakis, Ioannis Sourgias, Alexandra V. Michailidou and Christos Vlachokostas
Gases 2025, 5(3), 18; https://doi.org/10.3390/gases5030018 - 5 Aug 2025
Abstract
The naturally occurring radioactive gas radon presents a major public health danger mainly affecting people who spend time in poorly ventilated buildings. The periodic table includes radon as a noble gas which forms through uranium decay processes in soil, rock, and water. The [...] Read more.
The naturally occurring radioactive gas radon presents a major public health danger mainly affecting people who spend time in poorly ventilated buildings. The periodic table includes radon as a noble gas which forms through uranium decay processes in soil, rock, and water. The accumulation of radon indoors in sealed or poorly ventilated areas leads to dangerous concentrations that elevate human health risks of lung cancer. The research examines environmental variables affecting radon concentration indoors by studying geothermal installations and their drilling activities, which potentially increase radon emissions. The study was conducted in the basement of the plumbing educational building at the Aristotle University of Thessaloniki to assess the potential impact of geothermal activity on indoor radon levels, as the building is equipped with a geothermal heating system. The key findings based on 150 days of continuous data showed that radon levels peak during the cold days, where the concentration had a mean value of 41.5 Bq/m3 and reached a maximum at about 95 Bq/m3. The reason was first and foremost poor ventilation and pressure difference. The lowest concentrations were on days with increased human activity with measures that had a mean value of 14.8 Bq/m3, which is reduced by about 65%. The results that are presented confirm the hypotheses and the study is making clear that ventilation and human activity are crucial in radon mitigation, especially on geothermal and energy efficient structures. Full article
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19 pages, 513 KiB  
Review
Recent Trends in Surgical Strategies of Early-Stage Gallbladder Cancer: A Narrative Review
by Junseo Choi, Ji Su Kim and Jun Suh Lee
J. Clin. Med. 2025, 14(15), 5483; https://doi.org/10.3390/jcm14155483 - 4 Aug 2025
Abstract
Background/Objectives: Gallbladder cancer (GBC) is a lethal malignancy curable only by surgical resection in early stages (Tis, T1, T2). Significant controversy exists regarding the optimal extent of surgery. This review summarizes recent trends and evidence on surgical strategies for Tis, T1, and T2 [...] Read more.
Background/Objectives: Gallbladder cancer (GBC) is a lethal malignancy curable only by surgical resection in early stages (Tis, T1, T2). Significant controversy exists regarding the optimal extent of surgery. This review summarizes recent trends and evidence on surgical strategies for Tis, T1, and T2 GBC to guide practice and research. Methods: This narrative review synthesizes recent literature on surgical management of Tis, T1a, T1b, and T2 GBC based on American Joint Committee on Cancer (AJCC) 8th edition staging. It examines simple vs. extended cholecystectomy (simple cholecystectomy (SC) vs. extended/radical cholecystectomy (EC/RC)), the role of lymphadenectomy (LND) and hepatectomy, and minimally invasive surgery (MIS). Results: Simple cholecystectomy is curative for Tis/T1a GBC. For T1b, regional LND is essential for staging/potential benefit, especially examining ≥5–6 nodes. Tumor size is critical; SC alone may suffice for T1b < 1 cm (low lymph node metastasis (LNM) risk), while EC/RC with LND is indicated for ≥1 cm (higher LNM risk). Routine hepatectomy for T1b lacks survival support. For T2 GBC, mandatory regional LND (≥6 nodes) is required for both T2a and T2b substages due to high LNM rates; T2b has higher LNM than T2a. Routine hepatectomy for T2 is debated; evidence suggests no routine benefit for T2a beyond LND, with conflicting findings for T2b. R0 resection is paramount. MIS is feasible for early stages in experienced hands. Conclusions: Management of early GBC is moving towards risk stratification. SC is standard for Tis/T1a. Adequate regional LND is crucial for T1b (especially ≥1 cm) and mandatory for T2 GBC. Routine hepatectomy, particularly for T2b, remains controversial. Tailored surgery prioritizes R0 resection and comprehensive LND, necessitating further standardized research. Full article
(This article belongs to the Special Issue Advances and Trends in Visceral and Gastrointestinal Surgery)
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10 pages, 236 KiB  
Review
The Concept of “Platinum Sensitivity” in Endometrial Cancer
by Shoji Nagao, Atsushi Fujikawa, Ryoko Imatani, Yoshinori Tani, Hirofumi Matsuoka, Naoyuki Ida, Junko Haraga, Chikako Ogawa, Keiichiro Nakamura and Hisashi Masuyama
Cancers 2025, 17(15), 2557; https://doi.org/10.3390/cancers17152557 - 2 Aug 2025
Viewed by 184
Abstract
The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum [...] Read more.
The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer—where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)—approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making—particularly regarding treatment sequencing and drug selection—remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies. Full article
(This article belongs to the Special Issue Endometrial Cancer—from Diagnosis to Management)
38 pages, 2337 KiB  
Article
Synthesis of Carboranyl-Containing β-Arylaliphatic Acids for Potential Application in BNCT
by Lana I. Lissovskaya and Ilya V. Korolkov
Molecules 2025, 30(15), 3250; https://doi.org/10.3390/molecules30153250 - 2 Aug 2025
Viewed by 239
Abstract
One of the promising research areas involving carborane derivatives is boron neutron capture therapy (BNCT). Due to the high boron atom content in carborane molecules, these compounds are considered potential candidates for BNCT-based cancer treatment. Despite ongoing studies on various biologically active carboranyl-containing [...] Read more.
One of the promising research areas involving carborane derivatives is boron neutron capture therapy (BNCT). Due to the high boron atom content in carborane molecules, these compounds are considered potential candidates for BNCT-based cancer treatment. Despite ongoing studies on various biologically active carboranyl-containing compounds, the search continues for substances that meet the stringent requirements of effective BNCT agents. In this study, the synthesis of carboranyl-containing derivatives of β-arylaliphatic acids is described, along with the investigation of their reactivity with primary and secondary amines, as well as with metals and their hydroxides. The molecular structures of the synthesized compounds were confirmed using Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, and mass spectrometry (LC-MS). Cytotoxicity of the water-soluble compound potassium 3-(2-isopropyl-1,2-dicarba-closo-dodecaboran-1-yl)-3-phenylpropanoate was evaluated using several cell lines, including HdFn and MCF-7. Full article
(This article belongs to the Section Organic Chemistry)
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22 pages, 6854 KiB  
Article
Profiling the Expression Level of a Gene from the Caspase Family in Triple-Negative Breast Cancer
by Anna Makuch-Kocka, Janusz Kocki, Jacek Bogucki, Przemysław Kołodziej, Monika Lejman, Karolina Szalast and Anna Bogucka-Kocka
Int. J. Mol. Sci. 2025, 26(15), 7463; https://doi.org/10.3390/ijms26157463 - 1 Aug 2025
Viewed by 123
Abstract
It is believed that caspases may play a significant role in the development of cancer, and the expression levels of genes encoding these proteins may influence the prognosis and clinical course of cancer. Taking into account the information presented, we examined the expression [...] Read more.
It is believed that caspases may play a significant role in the development of cancer, and the expression levels of genes encoding these proteins may influence the prognosis and clinical course of cancer. Taking into account the information presented, we examined the expression profiles of 11 genes from the caspase family in patients diagnosed with triple-negative breast cancer (TNBC). We qualified 29 patients with TNBC. A fragment of the tumor and a fragment of normal tissue surrounding the tumor were collected from each patient. Then, RNA was isolated, and the reverse transcription process was performed. The expression levels of caspase family genes were determined using the real-time PCR method. The obtained data were correlated with clinical data and compared with data from the Cancer Genome Atlas database using the Breast Cancer Gene Expression Miner v4.8 and Ualcan. Based on the results of the conducted research, it can be assumed that the levels of expression of caspase family genes may be correlated with the clinical course of cancer in patients with TNBC, and further research may indicate that profiling the expression levels of these genes may be used in selecting personalized treatment methods. Full article
(This article belongs to the Special Issue Molecular Genetics of Breast Cancer—Recent Progress)
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38 pages, 1308 KiB  
Review
Mitochondrial Metabolomics in Cancer: Mass Spectrometry-Based Approaches for Metabolic Rewiring Analysis and Therapeutic Discovery
by Yuqing Gao, Zhirou Xiong and Xinyi Wei
Metabolites 2025, 15(8), 513; https://doi.org/10.3390/metabo15080513 - 31 Jul 2025
Viewed by 174
Abstract
Mitochondria, pivotal organelles in cellular metabolism and energy production, have emerged as critical players in the pathogenesis of cancer. This review outlines the progress in mitochondrial profiling through mass spectrometry-based metabolomics and its applications in cancer research. We provide unprecedented insights into the [...] Read more.
Mitochondria, pivotal organelles in cellular metabolism and energy production, have emerged as critical players in the pathogenesis of cancer. This review outlines the progress in mitochondrial profiling through mass spectrometry-based metabolomics and its applications in cancer research. We provide unprecedented insights into the mitochondrial metabolic rewiring that fuels tumorigenesis, metastasis, and therapeutic resistance. The purpose of this review is to provide a comprehensive guide for the implementation of mitochondrial metabolomics, integrating advanced methodologies—including isolation, detection, and data integration—with insights into cancer-specific metabolic rewiring. We first summarize current methodologies for mitochondrial sample collection and pretreatment. Furthermore, we then discuss the recent advancements in mass spectrometry-based methodologies that facilitate the detailed profiling of mitochondrial metabolites, unveiling significant metabolic reprogramming associated with tumorigenesis. We emphasize how recent technological advancements have addressed longstanding challenges in the field and explore the role of mitochondrial metabolism-driven cancer development and progression for novel drug discovery and translational research applications in cancer. Collectively, this review delineates emerging opportunities for therapeutic discovery and aims to establish a foundation for future investigations into the therapeutic modulation of mitochondrial pathways in cancer, thereby paving the way for innovative diagnostic and therapeutic approaches targeting mitochondrial pathways. Full article
(This article belongs to the Topic Overview of Cancer Metabolism)
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15 pages, 835 KiB  
Review
Optimising Exercise for Managing Chemotherapy-Induced Peripheral Neuropathy in People Diagnosed with Cancer
by Dhiaan Sidhu, Jodie Cochrane Wilkie, Jena Buchan and Kellie Toohey
Cancers 2025, 17(15), 2533; https://doi.org/10.3390/cancers17152533 - 31 Jul 2025
Viewed by 395
Abstract
Background: Chemotherapy-induced peripheral neuropathy is a common and debilitating side effect of cancer treatment. While exercise has shown promise in alleviating this burden, it remains underutilised in clinical practice due to the lack of accessible, clinician-friendly guidance. Aim: This review aimed to synthesise [...] Read more.
Background: Chemotherapy-induced peripheral neuropathy is a common and debilitating side effect of cancer treatment. While exercise has shown promise in alleviating this burden, it remains underutilised in clinical practice due to the lack of accessible, clinician-friendly guidance. Aim: This review aimed to synthesise current evidence on exercise interventions for managing chemotherapy-induced peripheral neuropathy and provide practical insights to support clinicians in integrating these approaches into patient care. Methods: A search was conducted across MEDLINE, CINAHL, and SPORTDiscus using keywords related to exercise and CIPN. Studies were included if they involved adults receiving neurotoxic chemotherapy and exercise-based interventions. Two authors independently screened studies and resolved conflicts with a third author. Study quality was assessed using the JBI Critical Appraisal Tools, and only studies meeting a minimum quality standard were included. A balanced sampling approach was employed. Data on study design, participant characteristics, interventions, and outcomes were extracted. Results: Eleven studies were included, covering various exercise modalities: multimodal (n = 5), yoga (n = 2), aerobic (n = 1), resistance (n = 1), balance (n = 1), and sensorimotor (n = 1). Exercise interventions, particularly multimodal exercise, significantly improved symptom severity, functionality, and quality of life (p < 0.05). The studies had high methodological quality, with randomised controlled trials scoring between 9/13 and 11/13, and quasi-experimental studies scoring 8/9 on JBI tools. Conclusions: This review highlights the significant benefits of exercise, especially multimodal exercise, for managing CIPN and provides guidance for integrating these strategies into clinical practice. Future research is needed to refine exercise prescriptions and develop standardised guidelines. Full article
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38 pages, 2158 KiB  
Review
Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies
by Mahmoud Zhra, Jasmine Hanafy Holail and Khalid S. Mohammad
Pharmaceuticals 2025, 18(8), 1140; https://doi.org/10.3390/ph18081140 - 31 Jul 2025
Viewed by 470
Abstract
Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding [...] Read more.
Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article
(This article belongs to the Section Biopharmaceuticals)
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17 pages, 475 KiB  
Review
The Rationale and Explanation for Rehabilitation Interventions in the Management of Treatment-Induced Trismus in People with Head and Neck Cancer: A Scoping Review of Randomized Controlled Trials
by Ernesto Anarte-Lazo, Ana Bravo-Vazquez, Carlos Bernal-Utrera, Daniel Torres-Lagares, Deborah Falla and Cleofas Rodríguez-Blanco
Medicina 2025, 61(8), 1392; https://doi.org/10.3390/medicina61081392 - 31 Jul 2025
Viewed by 431
Abstract
Background and objectives: Trismus is a frequent and debilitating complication in people with head and neck cancer (HNC) which leads to significant functional limitations and reduced quality of life. Rehabilitation interventions are commonly recommended to manage or prevent trismus. However, in many [...] Read more.
Background and objectives: Trismus is a frequent and debilitating complication in people with head and neck cancer (HNC) which leads to significant functional limitations and reduced quality of life. Rehabilitation interventions are commonly recommended to manage or prevent trismus. However, in many randomized controlled trials (RCTs), the theoretical justification for these interventions is poorly articulated, and the underlying biological or physiological mechanisms are not described in detail, limiting our understanding of why certain treatments may (or may not) work. This review aimed to identify and analyze how RCTs report the rationale for rehabilitation interventions and the explanations used to manage this population. Materials and Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. Five databases (PubMed, PEDro, Web of Science, Scopus, and EMBASE) were searched up to May 2025 for RCTs evaluating rehabilitation interventions for the management or prevention of treatment-induced trismus in patients with HNC. Data were extracted and synthesized narratively, focusing on the type of intervention, the rationale for its use, and the proposed mechanisms of action. Results: Of 2215 records identified, 24 RCTs met the inclusion criteria. Thirteen studies focused on preventive interventions—primarily exercise therapy—while the remainder addressed established trismus using exercise, manual therapy, electrotherapy, or combined treatment modalities. The rationales provided for intervention selection were heterogeneous and often lacked depth, with most studies justifying interventions based on their potential to improve mouth opening or reduce fibrosis but rarely grounding these claims in detailed pathophysiological models. Only half of the studies provided any mechanistic explanation for the intervention’s effects, and these were typically generic or speculative. Conclusions: RCTs investigating rehabilitation interventions for treatment-induced trismus in patients with HNC frequently lack comprehensive rationales and mechanistic explanations for their interventions. This gap limits the ability to refine and optimize treatment approaches, as the underlying processes driving clinical improvements remain poorly understood. Future research should be guided by theoretical models and include objective outcomes to better elucidate the mechanisms of action of interventions to inform clinical practice. Full article
(This article belongs to the Special Issue Advances in Head and Neck Cancer Management)
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