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Recent Progress in Small Molecule Fluorescent Probes for Imaging and Diagnosis of Liver Injury -
The Use of Particle Radiotherapy and Radiation Sensitizers for Treatment of Chordomas: A Narrative Review -
Current Pharmacotherapies for Alcohol Use Disorder in Italy: From Neurobiological Targets to Clinical Practice
Journal Description
Targets
Targets
is an international, peer-reviewed, open access journal on chemical measurement science, biology, material science, pharmacy, clinical diagnostics, molecular medicine and biomedicine published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 24.8 days after submission; acceptance to publication is undertaken in 4.7 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
- Companion journal: Sensors.
- Journal Clusters of Oncology: Cancers, Current Oncology, Onco and Targets.
Latest Articles
Navigating the Molecular and Cellular Landscape of Breast Cancer in India: From Unique Pathogenesis to the Promise of Personalized Medicine and Future Technologies
Targets 2025, 3(4), 38; https://doi.org/10.3390/targets3040038 - 15 Dec 2025
Abstract
Breast cancer is a substantial and growing public health issue in India, with epidemiological data demonstrating distinct and often severe disease characteristics in contrast to Western countries. Contrary to the global trend, Indian women frequently develop the disease at an earlier age and
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Breast cancer is a substantial and growing public health issue in India, with epidemiological data demonstrating distinct and often severe disease characteristics in contrast to Western countries. Contrary to the global trend, Indian women frequently develop the disease at an earlier age and tend to present with more advanced stages, emphasizing important variations in disease pathophysiology. This review compiles and critically evaluates the current literature to describe the specific pathophysiology of breast cancer in the Indian population. We investigate the unique cellular and molecular landscapes, evaluate the impact of specific Indian demographic and genetic features, and highlight crucial gaps in knowledge, diagnostic tools, and therapeutic approaches. The assessment reveals a molecular landscape determined by the incidence of specific tumor subtypes; triple-negative breast cancer, for instance, is frequently diagnosed in younger women, and genetic profiling research suggests variations in its susceptibility genes and mutation patterns when compared to global populations. While this paper brings together recent advancements, it highlights the challenges of adopting global diagnostic and treatment guidelines in the Indian healthcare system. These challenges are largely due to variances and specific demographic and socioeconomic discrepancies that create substantial hurdles for timely diagnosis and patient care. We highlight significant gaps, such as the need for more complete multi-omics profiling of Indian patient cohorts, an absence of uniform and readily available screening programs, and shortcomings in healthcare infrastructure and qualified oncology experts. Furthermore, the review highlights the crucial need for therapeutic strategies tailored to the distinct genetic and demographic profiles of Indian breast cancer patients. We present significant strategies for addressing these challenges, with a focus on integrating multi-omics data and clinical characteristics to gain deeper insight into the underlying causes of the disease. Promising avenues include using artificial intelligence and advancements in technology to improve diagnostics, developing indigenous and affordable treatment options, and establishing context-specific research frameworks for the Indian population. This review also underlines the necessity for personalized strategies to improve breast cancer outcomes in India.
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(This article belongs to the Special Issue Comprehending Molecular Targets: Mechanisms and Actions in Drug Development)
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Fatal Early Toxicity After Allogeneic Stem Cell Transplantation in Heavily Pretreated Follicular Lymphoma: Clinical Decision-Making Between Bispecific Antibodies and CAR T-Cell Therapy
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Martina Canichella, Raffaella Cerretti, Monika Malgorzata Trawinska, Mariagiovanna Cefalo, Luca Cupelli, Carla Mazzone, Alessandra Checcoli, Alice Di Rocco, Paolo de Fabritiis and Elisabetta Abruzzese
Targets 2025, 3(4), 37; https://doi.org/10.3390/targets3040037 - 10 Dec 2025
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For patients with relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior lines of therapy, T-cell-redirecting therapies—including the bispecific CD3xCD20 antibody (BsAbs) mosunetuzumab (mosu) and chimeric antigen receptor T-cell (CAR-T) therapies such as axicabtagene ciloleucel (axi-cel), lisocabtagen maraleucel (liso-cel), and tisagenlecleucel (tisa-cel)—are approved by
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For patients with relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior lines of therapy, T-cell-redirecting therapies—including the bispecific CD3xCD20 antibody (BsAbs) mosunetuzumab (mosu) and chimeric antigen receptor T-cell (CAR-T) therapies such as axicabtagene ciloleucel (axi-cel), lisocabtagen maraleucel (liso-cel), and tisagenlecleucel (tisa-cel)—are approved by the FDA and EMA. Treatment selection should consider patient-related factors, prior therapeutic exposure, and toxicity profiles. We describe the 20-year history of a patient with R/R FL. At the fourth relapse, both BsAbs and CAR-T cells were available; however, due to the cumulative toxic burden and the high risk of cytopenias, mosu was selected as the preferred option. During mosu, the patient developed pure red cell aplasia unrelated to infections. Despite achieving a partial response after eight cycles of mosu, this complication led to the decision to proceed with allogeneic stem cell transplantation (allo-HSCT). The course was ultimately complicated by severe early toxicity with massive hemoptysis, acute respiratory failure, and hemorrhagic alveolitis, resulting in a fatal outcome. This case illustrates the delicate balance required in selecting between BsAbs and CAR-T therapy in R/R FL. Contributing factors to the patient’s fragility included profound immune status, transfusion-dependent red cell aplasia, prior cumulative chemotherapy, and pulmonary toxicity associated with conditioning regimens. The case underscores the importance of individualized treatment strategies and suggests that earlier integration of novel T-cell-redirecting therapies may mitigate cumulative toxicity and infection risk. Individualized therapeutic planning is critical in heavily pretreated R/R FL. In select cases, bridging strategies using BsAbs can provide disease control and facilitate transplantation. Still, careful assessment of patient fitness, marrow reserve, and cumulative toxicity is essential to minimize the risk of fatal complications.
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Open AccessArticle
Long-Term Outcomes of Co-Testing with 3-Type HPV mRNA (16/18/45) and Cytology in Women Under 40: A Real-World Cohort from Northern Norway (8–10 Years of Follow-Up)
by
Marie Bostrøm, Gunnar Skov Simonsen and Sveinung Wergeland Sørbye
Targets 2025, 3(4), 36; https://doi.org/10.3390/targets3040036 - 6 Dec 2025
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In Norway, organized cervical cancer screening was cytology-based until 2023, and women screened in 2013–2015 were largely unvaccinated. We conducted a retrospective, population-based cohort study to assess whether co-testing with a 3-type HPV mRNA assay improves detection of high-grade cervical lesions in women
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In Norway, organized cervical cancer screening was cytology-based until 2023, and women screened in 2013–2015 were largely unvaccinated. We conducted a retrospective, population-based cohort study to assess whether co-testing with a 3-type HPV mRNA assay improves detection of high-grade cervical lesions in women < 40 years. Among 11,395 women screened in Northern Norway and followed for 8–10 years, 2807 formed a co-testing cohort (ThinPrep cytology plus PreTect SEE; HPV16/18/45) and 8588 formed a cytology-only cohort. The endpoint was histologically confirmed CIN2+. Sensitivity for CIN2+ was 63.7% with cytology alone and 71.0% with co-testing (absolute +7.3 percentage points; p = 0.034). In the co-testing cohort, HPV mRNA was detected in 10.2% of women, of whom 46.0% developed CIN2+, while CIN2+ risk in HPV mRNA-negative women was 5.2%. Co-testing produced wide risk gradients: CIN2+ risk was 58.3% in double-positive women (HPV mRNA-positive and ASC-US+) and 3.3% in double-negative women (HPV mRNA-negative and normal cytology), with no cervical cancers observed in the latter group. In this cytology-based, largely unvaccinated setting, co-testing with a 3-type HPV mRNA assay improved detection performance and long-term risk stratification in women < 40 years, supporting its use as a quality-assurance and triage tool within organized screening programs.
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Open AccessArticle
Discovery of Novel FGFR1 Inhibitors via Pharmacophore Modeling and Scaffold Hopping: A Screening and Optimization Approach
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Xingchen Ji, Jiahua Tao, Na Zhang, Linxin Wang, Xiyi Zheng and Lianxiang Luo
Targets 2025, 3(4), 35; https://doi.org/10.3390/targets3040035 - 27 Nov 2025
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Aberrant activation of fibroblast growth factor receptor 1 (FGFR1) drives tumor progression in multiple cancer types, yet existing FGFR1 inhibitors suffer from suboptimal target selectivity and dose-limiting toxicities. This study describes an integrated computational approach for the identification of novel FGFR1 inhibitors. We
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Aberrant activation of fibroblast growth factor receptor 1 (FGFR1) drives tumor progression in multiple cancer types, yet existing FGFR1 inhibitors suffer from suboptimal target selectivity and dose-limiting toxicities. This study describes an integrated computational approach for the identification of novel FGFR1 inhibitors. We established a computational pipeline incorporating ligand-based pharmacophore modeling, multi-tiered virtual screening with hierarchical docking (HTVS/SP/XP), and MM-GBSA binding energy calculations to evaluate interactions within the FGFR1 kinase domain. From an initial library of 9019 anticancer compounds, three hit compounds exhibited superior FGFR1 binding affinity compared to the reference ligand 4UT801. Scaffold hopping was performed to generate 5355 structural derivatives, among which candidate compounds 20357a–20357c showed improved bioavailability and reduced toxicity as predicted by absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. Molecular dynamics (MD) simulations validated stable binding modes and favorable interaction energies for these candidates. Collectively, our study identifies structurally novel FGFR1 inhibitors with optimized pharmacodynamic and safety profiles, thereby advancing targeted anticancer drug discovery.
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Open AccessReview
Galectin-3: A Multitasking Protein Linking Cardiovascular Diseases, Immune Disorders and Beyond
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Mariarosaria Morello, Gisella Titolo, Saverio D’Elia, Silvia Caiazza, Ettore Luisi, Achille Solimene, Chiara Serpico, Andrea Morello, Francesco Natale, Paolo Golino, Plinio Cirillo and Giovanni Cimmino
Targets 2025, 3(4), 34; https://doi.org/10.3390/targets3040034 - 15 Nov 2025
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In recent decades, the novel role of Galectin-3 (Gal-3) in both physiological and pathological conditions has emerged. Gal-3 is a key protein involved in immunity, inflammation, cell adhesion, proliferation, differentiation, and apoptosis. Its physiological role is crucial for the regulation of these cellular
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In recent decades, the novel role of Galectin-3 (Gal-3) in both physiological and pathological conditions has emerged. Gal-3 is a key protein involved in immunity, inflammation, cell adhesion, proliferation, differentiation, and apoptosis. Its physiological role is crucial for the regulation of these cellular functions. In pathological settings, elevated levels of Gal-3 are associated with diseases such as cancer, heart failure, and fibrotic diseases, making it an important diagnostic and prognostic biomarker in these conditions. It seems that Gal-3 acts as a bridge between different diseases. Because of its pro-inflammatory and pro-tumorigenic properties, it connects atherosclerosis and cancer, regulating inflammation, cell proliferation, immune evasion, angiogenesis and survival in both diseases. Specifically, in atherosclerosis, Gal-3 promotes plaque formation by driving inflammation, oxidative stress, lipid deposition, and vascular cell migration. In cancer, Gal-3 influences tumor growth and metastasis by modulating an immunosuppressive tumor microenvironment, increasing cell survival, and enhancing cell–matrix and cell–cell interactions. Moreover, by stimulating fibroblasts, Gal-3 favors matrix deposition and tissue fibrosis that together with the inflammatory properties contributes to adverse ventricular remodeling leading to heart failure. Finally, taking into account its role in pathogen recognition and immune cells (B and T cells) modulation, Gal-3 might be a critical factor in host defense, disease progression, and the development of autoimmune conditions. Thus, targeting Gal-3 might be a promising therapeutic strategy to pursue for management of different pathological scenarios.
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Open AccessArticle
Simulated Pharmacokinetic Compatibility of Tamoxifen and Estradiol: Insights from a PBPK Model in Hormone-Responsive Breast Cancer
by
Beatriz Gomes and Nuno Vale
Targets 2025, 3(4), 33; https://doi.org/10.3390/targets3040033 - 30 Oct 2025
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Although traditionally contraindicated, the coadministration of tamoxifen and estradiol may hold clinical relevance in specific contexts, particularly in breast cancer survivors with premature menopause and a high risk of osteoporosis, thereby justifying the need to re-evaluate this therapeutic combination. This study presents an
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Although traditionally contraindicated, the coadministration of tamoxifen and estradiol may hold clinical relevance in specific contexts, particularly in breast cancer survivors with premature menopause and a high risk of osteoporosis, thereby justifying the need to re-evaluate this therapeutic combination. This study presents an innovative physiologically based pharmacokinetic (PBPK) modeling approach to evaluate the coadministration of tamoxifen and estradiol in women with breast cancer and a high risk of osteoporosis. Using GastroPlus® software, PBPK models were developed and validated for both drugs, based on physicochemical and kinetic data obtained from the literature and, where necessary, supplemented by estimates generated in ADMET Predictor®. The simulations considered different hormonal profiles (pre and postmenopausal) and therapeutic regimens, evaluating potential interactions mediated by the CYP3A4 enzyme. Analysis of the pharmacokinetic parameters (F, Cmax, Tmax and AUC) revealed strong agreement between the simulated and experimental values, with prediction errors of less than twofold. The drug interaction studies, carried out in dynamic and stationary modes, indicated that estradiol does not significantly alter the pharmacokinetics of tamoxifen, even at increasing doses or in enlarged virtual populations. These results represent the first in silico evidence that, under certain conditions, the concomitant use of estradiol does not compromise the pharmacokinetic efficacy of tamoxifen. Although the study is computational, it provides a solid scientific basis for re-evaluating this therapeutic combination and proposes a pioneering model for personalized strategies in complex oncological contexts. All simulations assumed average enzyme abundance/activity without CYP polymorphism parameterization; findings are restricted to parent-tamoxifen pharmacokinetics and do not infer metabolite (e.g., endoxifen) exposure or phenotype effects.
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Open AccessReview
Extracellular Vesicle-Associated miRNAs in Cornea Health and Disease: Diagnostic Potential and Therapeutic Implications
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Nagendra Verma, Swati Arora, Anurag Kumar Singh and Amrendra Kumar
Targets 2025, 3(4), 32; https://doi.org/10.3390/targets3040032 - 17 Oct 2025
Cited by 1
Abstract
Extracellular Vesicle-associated microRNAs (EV-miRNAs) are emerging as pivotal regulators of corneal health and disease, holding exceptional promise for transforming both diagnostics and therapeutics. These vesicles carry distinct miRNA signatures in biofluids such as tears, offering a powerful, non-invasive approach for early detection, risk
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Extracellular Vesicle-associated microRNAs (EV-miRNAs) are emerging as pivotal regulators of corneal health and disease, holding exceptional promise for transforming both diagnostics and therapeutics. These vesicles carry distinct miRNA signatures in biofluids such as tears, offering a powerful, non-invasive approach for early detection, risk stratification, and dynamic monitoring of corneal disorders. In addition, EV-miRNAs act as key mediators of critical biological processes, including inflammation, fibrosis, and tissue repair. Consequently, they represent attractive therapeutic targets; for example, engineered EVs loaded with miRNA mimics or inhibitors can precisely modulate these pathways to promote regeneration and suppress disease progression. Yet, despite this considerable promise, the translation of EV-miRNA research into clinical practice remains constrained by several challenges. Topmost among these are the lack of standardized EV isolation methods, variability in miRNA quantification, and the pressing need for regulatory frameworks tailored to the complexity of these biological therapeutics. Addressing these barriers is essential to ensure reproducibility, scalability, and safety in clinical applications. Accordingly, this review synthesizes current knowledge on EV-miRNA profiles in corneal diseases, critically evaluates their diagnostic and therapeutic potential, and highlights strategies to overcome existing technical and regulatory limitations. Ultimately, the successful integration of EV-miRNA-based approaches into personalized medicine frameworks could revolutionize the management of corneal diseases and substantially improve patient outcomes.
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(This article belongs to the Topic Biomarkers of Disease: Discovery and Clinical Applications)
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Open AccessReview
Integrating Nanotechnology and Artificial Intelligence for Early Detection and Prognostication of Glioblastoma: A Translational Perspective
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Meghraj Vivekanand Suryawanshi, Imtiyaz Bagban and Akshata Yashwant Patne
Targets 2025, 3(4), 31; https://doi.org/10.3390/targets3040031 - 14 Oct 2025
Cited by 1
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Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. This review explains the connections between the genesis and progression of GBM and particular cellular tumorigenic mechanisms, such as angiogenesis, invasion, migration, growth factor overexpression, genetic instability, and apoptotic disorders,
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Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. This review explains the connections between the genesis and progression of GBM and particular cellular tumorigenic mechanisms, such as angiogenesis, invasion, migration, growth factor overexpression, genetic instability, and apoptotic disorders, as well as possible therapeutic targets that help predict the course of the disease. Glioblastoma multiforme (GBM) diagnosis relies heavily on histopathological features, molecular markers, extracellular vesicles, neuroimaging, and biofluid-based glial tumor identification. In order to improve miRNA stability and stop the proliferation of cancer cells, nanoparticles, magnetic nanoparticles, contrast agents, gold nanoparticles, and nanoprobes are being created for use in cancer treatments, neuroimaging, and biopsy. Targeted nanoparticles can boost the strength of an MRI signal by about 28–50% when compared to healthy tissue or controls in a preclinical model like mouse lymph node metastasis. Combining the investigation of CNAs and noncoding RNAs with deep learning-driven global profiling of genes, proteins, RNAs, miRNAs, and metabolites presents exciting opportunities for creating new diagnostic markers for malignancies of the central nervous system. Artificial intelligence (AI) advances precision medicine and cancer treatment by enabling the real-time analysis of complex biological and clinical data through wearable sensors and nanosensors; optimizing drug dosages, nanomaterial design, and treatment plans; and accelerating the development of nanomedicine through high-throughput testing and predictive modeling.
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Open AccessReview
The Expanding E3 Ligase-Ligand Landscape for PROTAC Technology
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Zhenzhen Li, Xiaoli Huang, Xuchi Zhao, Yunxiu Zhang and Ping Li
Targets 2025, 3(4), 30; https://doi.org/10.3390/targets3040030 - 27 Sep 2025
Abstract
Proteolysis-targeting chimeras (PROTACs) are a transformative therapeutic modality that co-opts the ubiquitin-proteasome system for selective protein degradation. To date, the development of PROTACs has been overwhelmingly dominated by the recruitment of four canonical E3 ligases: CRBN, VHL, MDM2, and IAP. This limited repertoire
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Proteolysis-targeting chimeras (PROTACs) are a transformative therapeutic modality that co-opts the ubiquitin-proteasome system for selective protein degradation. To date, the development of PROTACs has been overwhelmingly dominated by the recruitment of four canonical E3 ligases: CRBN, VHL, MDM2, and IAP. This limited repertoire represents a critical bottleneck, restricting the scope of degradable proteins and potential therapeutic applications. Addressing this challenge, recent years have witnessed a surge in the successful recruitment of novel E3 ligases. This review provides a dedicated and comprehensive summary of this progress, focusing exclusively on the emerging E3 ligases and their cognate ligands reported for PROTAC technology outside of the well-established quartet. We detail their discovery and strategic application, highlighting how this rapidly expanding toolbox promises to overcome existing limitations and unlock the full potential of targeted protein degradation.
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(This article belongs to the Special Issue Comprehending Molecular Targets: Mechanisms and Actions in Drug Development)
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Open AccessArticle
Contrast-Enhanced Mammography as a Functional Biomarker in Breast Cancer: Correlation of Enhancement Patterns with Ki-67 and Histological Grade
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Marina Balbino, Manuela Montatore, Federica Masino, Antonietta Ancona, Francesca Anna Carpagnano, Giulia Capuano, Riccardo Guglielmi and Giuseppe Guglielmi
Targets 2025, 3(3), 29; https://doi.org/10.3390/targets3030029 - 17 Sep 2025
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Background: Contrast-Enhanced Spectral Mammography (CESM) combines anatomical and functional imaging, showing promise in breast cancer diagnosis. Despite well-established lesion detection accuracy, few studies have investigated the link between CESM enhancement patterns and tumor aggressiveness biomarkers. Methods: We retrospectively evaluated 100 patients (mean age
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Background: Contrast-Enhanced Spectral Mammography (CESM) combines anatomical and functional imaging, showing promise in breast cancer diagnosis. Despite well-established lesion detection accuracy, few studies have investigated the link between CESM enhancement patterns and tumor aggressiveness biomarkers. Methods: We retrospectively evaluated 100 patients (mean age 59.5 years) undergoing CESM with complete histopathological data. Lesions were categorized by enhancement intensity (high, medium, low) and contrast homogeneity (homogeneous vs. heterogeneous), correlated with Ki-67 index and histological grade. Results: Lesion size measured by CESM closely matched histology (mean 2.16 cm vs. 2.25 cm). Mass-like lesions corresponded mainly to invasive ductal carcinoma, while non-mass patterns aligned with lobular or in situ carcinomas. Enhancement intensity correlated moderately with Ki-67 (Spearman ρ = 0.56, p < 0.001), and contrast heterogeneity showed a weaker but significant correlation with tumor grade (ρ = 0.22, p < 0.05). Conclusions: CESM accurately assesses tumor size and provides functional insight into tumor biology. Enhancement intensity may serve as a non-invasive proliferation marker, while contrast heterogeneity offers additional prognostic data, supporting CESM’s role in personalized breast cancer management.
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Open AccessReview
The Use of Particle Radiotherapy and Radiation Sensitizers for Treatment of Chordomas: A Narrative Review
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Aarti Kishore Jain, Sahdev S. Baweja, Beatrice Campilan, Madison J. Michles, Aviva Berkowitz and Patricia L. Zadnik Sullivan
Targets 2025, 3(3), 28; https://doi.org/10.3390/targets3030028 - 15 Aug 2025
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Chordomas are primary tumors of the skull base and vertebral column typically derived from the notochord. Treatment options consist of surgical resection, radiotherapy, and chemotherapy. This study reviews clinical trials focused on radiotherapy techniques, such as photon therapy and carbon ion radiotherapy, as
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Chordomas are primary tumors of the skull base and vertebral column typically derived from the notochord. Treatment options consist of surgical resection, radiotherapy, and chemotherapy. This study reviews clinical trials focused on radiotherapy techniques, such as photon therapy and carbon ion radiotherapy, as well as the concomitant use of radia-tion sensitizers. We completed a literature review on all published clinical trials on the usage of photon, proton, and carbon ion radiotherapy (CIRT) for chordoma in adults and all published literature on radiation sensitizers used for treatment in chordoma from 2000 to 2025. We reviewed all nine current clinical trials on radiotherapy for chordoma in adults. All clinical trials were able to achieve an overall survival rate above 50% at 3-year follow-up. Seven publications were found on the use of radiation sensitizers for chordomas, both in vitro and in vivo. The completed clinical trials evaluate the effectiveness of proton, photon, and CIRT for treatment of the skull base, spine, and sacral chordoma. Current trials continue these efforts and compare the different radiotherapies and determine appropriate doses. Research on radiation sensitizers for chordomas shows various therapies, ranging from hyperthermia to pharmaceutical options, that require further study.
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Open AccessReview
Approaches for Identifying LncRNA-Associated Proteins for Therapeutic Targets and Cancer Biomarker Discovery
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Mohammad Shabir Hussain, Puneet Vij, Sudhir Kotnala, Shadab Ahmad, Subhash C. Chauhan and Manish K. Tripathi
Targets 2025, 3(3), 27; https://doi.org/10.3390/targets3030027 - 11 Aug 2025
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Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and cellular signaling in cancer. Their functions are primarily mediated through interactions with specific protein partners that modulate chromatin structure, epigenetic remodeling, transcription, and signal transduction. In this review, we
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Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and cellular signaling in cancer. Their functions are primarily mediated through interactions with specific protein partners that modulate chromatin structure, epigenetic remodeling, transcription, and signal transduction. In this review, we explore reports and strategies for the proteomic characterization of lncRNA-associated proteins, particularly emphasizing high-throughput liquid chromatography–mass spectrometry (LC-MS)-based techniques. Affinity-based methods such as RNA pull-down, ChIRP MS, RAP-MS, BioID-MS, and SILAC-MS enable sensitive and specific mapping of lncRNA and protein complexes. These approaches reveal cancer-specific proteomic signatures, post-translational modifications, and mechanistic insights into tumor biology. The use of label-free quantification, bituminization, and crosslinking strategies further enhances the resolution of dynamic RNA–protein networks. Validation tools following bioinformatic analyses, such as Western blotting, immunohistochemistry, immunofluorescence, and ELISA, are used to prioritize and confirm findings. Candidate biomarkers from hepatocellular carcinoma to colorectal and prostate cancers, profiling lncRNA-associated proteins, hold promise for identifying clinically actionable biomarkers and therapeutic targets. This review highlights the translational relevance of lncRNA protein studies and advocates for their broader adoption in oncological research. In LC-MS workflows, proteins bound to lncRNAs are enzymatically digested into peptides, separated via nano-LC, and analyzed using high-resolution tandem MS. Label-free or isotope-labeled methods quantify differential enrichment, followed by bioinformatics-driven pathway annotation.
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Open AccessReview
Skeletal Health in Pituitary and Neuroendocrine Diseases: Prevention and Treatments of Bone Fragility
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Flavia Costanza, Antonella Giampietro, Laura De Marinis, Antonio Bianchi, Sabrina Chiloiro and Alfredo Pontecorvi
Targets 2025, 3(3), 26; https://doi.org/10.3390/targets3030026 - 8 Aug 2025
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Bone loss is common in patients affected by pituitary and neuroendocrine disorders as both hormone excess and hormone deficiency can affect bone structure. There is increasing evidence that pituitary hormones directly influence bone cells turnover by bypassing endocrine organs. Osteopenia, osteoporosis, and vertebral
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Bone loss is common in patients affected by pituitary and neuroendocrine disorders as both hormone excess and hormone deficiency can affect bone structure. There is increasing evidence that pituitary hormones directly influence bone cells turnover by bypassing endocrine organs. Osteopenia, osteoporosis, and vertebral fractures often result from these skeletal changes; however, diagnosing and managing bone frailty in pituitary and neuroendocrine disorders is still challenging because of the unpredictable outcomes in terms of fracture risk, even after the improvement of pituitary dysfunction, and the limited evidence for the use of bone-active drugs in these pathologies. The use of vitamin D supplements for fracture prevention is still debated in these secondary forms of bone frailty, although some studies have shown similar benefits to those derived in the general population. This review offers an overview on the characteristics of bone fragility in different pituitary and neuroendocrine diseases, and focuses on the prevention and treatment of skeletal disorders with bone-active drugs and vitamin D formulations currently available in this setting.
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Open AccessReview
Bacteriophages: Potential Candidates for the Dissemination of Antibiotic Resistance Genes in the Environment
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Shahid Sher, Husnain Ahmad Khan, Zaman Khan, Muhammad Sohail Siddique, Dilara Abbas Bukhari and Abdul Rehman
Targets 2025, 3(3), 25; https://doi.org/10.3390/targets3030025 - 22 Jul 2025
Abstract
The invention of antibacterial agents (antibiotics) was a significant event in the history of the human race, and this invention changed the way in which infectious diseases were cured; as a result, many lives have been saved. Recently, antibiotic resistance has developed as
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The invention of antibacterial agents (antibiotics) was a significant event in the history of the human race, and this invention changed the way in which infectious diseases were cured; as a result, many lives have been saved. Recently, antibiotic resistance has developed as a result of excessive use of antibiotics, and it has become a major threat to world health. ARGs are spread across biomes and taxa of bacteria via lateral or horizontal gene transfer (HGT), especially via conjugation, transformation, and transduction. This review concerns transduction, whereby bacteriophages or phages facilitate gene transfer in bacteria. Bacteriophages are just as common and many times more numerous than their bacterial prey, and these phages are much more influential in controlling the population of bacteria. It is estimated that 25% of overall genes of Escherichia coli have been copied by other species of bacteria due to the HGT process. Transduction may take place via a generalized or specialized mechanism, with phages being ubiquitous in nature. Phage and virus-like particle (VLP) metagenomics have uncovered the emergence of ARGs and mobile genetic elements (MGEs) of bacterial origins. These genes, when transferred to bacteria through transduction, confer resistance to antibiotics. ARGs are spread through phage-based transduction between the environment and bacteria related to people or animals, and it is vital that we further understand and tackle this mechanism in order to combat antimicrobial resistance.
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(This article belongs to the Special Issue Small-Molecule Antibiotic Drug Development)
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Open AccessReview
Current Pharmacotherapies for Alcohol Use Disorder in Italy: From Neurobiological Targets to Clinical Practice
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Andrea Mastrostefano, Giuseppe Greco, Chiara De Bacco, Flavio Davini, Giacomo Polito, Edoardo Carnevale, Giuseppe Anastasi and Sergio Terracina
Targets 2025, 3(3), 24; https://doi.org/10.3390/targets3030024 - 11 Jul 2025
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Alcohol is a prevalent psychoactive substance and a risk factor for developing injuries and non-communicable diseases, representing a significant health and economic burden. Alcohol involves numerous molecular pathways. Its metabolism is regulated by alcohol dehydrogenases and aldehyde dehydrogenases; it also stimulates cholinergic interneurons,
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Alcohol is a prevalent psychoactive substance and a risk factor for developing injuries and non-communicable diseases, representing a significant health and economic burden. Alcohol involves numerous molecular pathways. Its metabolism is regulated by alcohol dehydrogenases and aldehyde dehydrogenases; it also stimulates cholinergic interneurons, increasing the sensitivity of 5-HT3 receptors, while chronic alcohol consumption alters the mesolimbic dopaminergic system involved in reward processing. The treatment of alcohol use disorder (AUD) is essential to manage complex patients, following an evidence-based approach. The aim of this narrative review is to provide a clear and practical summary to support and assist healthcare professionals in the Italian context. Approved pharmacological treatments for AUD include oral naltrexone and acamprosate, sodium oxybate, disulfiram, and nalmefene. Off-label therapies include baclofen, topiramate, gabapentin, pregabalin, ondansetron, and cytisine. A more informed clinical and practical approach that understands the altered neuronal signaling pathways is essential for offering effective, efficient, appropriate, and safe therapeutic algorithms for complex patients with alcohol use disorder. A comprehensive framework should include integrated treatments with a personalized approach.
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Open AccessReview
Natural Products Acting as Senolytics and Senomorphics Alleviate Cardiovascular Diseases by Targeting Senescent Cells
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Hejing Tang, Xu Zhang, Senyang Hu, Yuhan Song, Wenhua Jin, Jianmin Zou, Yan Zhang, Jiayue Guo, Peng An, Junjie Luo, Pengjie Wang, Yongting Luo and Yinhua Zhu
Targets 2025, 3(3), 23; https://doi.org/10.3390/targets3030023 - 25 Jun 2025
Cited by 2
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Taken together, cardiovascular diseases (CVDs) have become one of the prime causes of the global disease burden. Aging is closely related to CVDs and is considered to be one of the crucial factors in the incidence of CVDs. In the process of aging,
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Taken together, cardiovascular diseases (CVDs) have become one of the prime causes of the global disease burden. Aging is closely related to CVDs and is considered to be one of the crucial factors in the incidence of CVDs. In the process of aging, cellular senescence is an important cause of CVDs such as atherosclerosis and atrial fibrillation. The treatment for CVDs by targeting senescent cells has been carried out in cellular models, animal experiments, and anti-aging clinical trials. Chemical approaches to regulate the fate of senescent cells by senolytics and senomorphics, which could selectively eliminate senescent cells or inhibit their senescence-associated secretory phenotype (SASP) secretion, have been increasingly explored. Importantly, many natural products with promising biological activity extracted from food or medicine–food homology have the above-mentioned effects. Furthermore, the identification of the target cells or target proteins of these natural products is of great significance for the indication of their mechanism of action, and it also lays a scientific foundation for the realization of precision nutrition intervention in the future. This review details how senescent cells affect CVDs, how natural products target senescent cells through nutritional intervention, and research methods for natural products in cardiovascular aging.
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Open AccessArticle
A Report on the Antidepressant-like Activity of Paullinia pinnata Methanol Leaf Extract in Mice and Possible Involvement of Monoaminergic Mechanisms
by
Raymond I. Ozolua, Muideen A. Ajibade, Dickson O. Uwaya, Abigail M. Akhigbemen and Israel O. Bolanle
Targets 2025, 3(2), 22; https://doi.org/10.3390/targets3020022 - 16 Jun 2025
Cited by 1
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In West Africa, Paullinia pinnata (P. pinnata) alcohol leaf extracts are used to treat disorders such as depression and anxiety with no documented scientific justification. We have therefore evaluated the potential anxiolytic and antidepressant effects of Paullinia pinnata methanol leaf extract
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In West Africa, Paullinia pinnata (P. pinnata) alcohol leaf extracts are used to treat disorders such as depression and anxiety with no documented scientific justification. We have therefore evaluated the potential anxiolytic and antidepressant effects of Paullinia pinnata methanol leaf extract (PPME) in mice, along with probable underlying mechanisms. Adult Swiss albino mice were administered 100, 200, and 400 mg/kg of PPME orally before subjecting them through elevated plus maze (EPM) and hole-board tests to assess the anxiolytic effect. The tail suspension test (TST) and the forced swim test (FST) were used to assess the antidepressant-like effects. Reserpine, labetalol, and risperidone were used to investigate probable mechanisms of action. In both FST and TST, the duration of immobility was considerably reduced by PPME. Conversely, PPME had no significant effect on the number of mice who dipped their heads into the hole-board or entered the EPM’s open arm. Mechanistic analysis revealed that in mice given labetalol or risperidone beforehand, PPME dramatically reduced the length of immobility and reversed ptosis and akinesia caused by reserpine. Our findings suggest that PPME possesses antidepressant-like, but not anxiolytic-like, effects in mice, and antidepressant action may involve enhancing noradrenergic and serotonergic mechanisms.
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Open AccessReview
Targeted Treatment Approaches for Gastrointestinal Metastases of Malignant Melanoma: Clinical Insights and Overcoming Drug Resistance
by
Tsvetelina Velikova, Marina Konaktchieva and Milena Peruhova
Targets 2025, 3(2), 21; https://doi.org/10.3390/targets3020021 - 11 Jun 2025
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Gastrointestinal metastases of malignant melanoma are relatively common and pose significant challenges to clinical management due to their complex presentation and resistance to therapy. Early detection and a multidisciplinary treatment approach are critical to improve outcomes. This review highlights targeted treatment strategies for
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Gastrointestinal metastases of malignant melanoma are relatively common and pose significant challenges to clinical management due to their complex presentation and resistance to therapy. Early detection and a multidisciplinary treatment approach are critical to improve outcomes. This review highlights targeted treatment strategies for gastrointestinal melanoma metastases, focusing on current therapeutic options and the mechanisms underlying drug resistance. Advances in immune checkpoint inhibitors (ICIs) and targeted therapies, such as BRAF and MEK inhibitors, have revolutionized melanoma treatment, yet their efficacy is often limited by the emergence of resistance mechanisms, including genetic mutations, tumor microenvironment factors, and immune escape. Herein, we explore potential resistance biomarkers for resistance and emerging targeting treatments targeting these pathways. Understanding the molecular and cellular mechanisms driving drug resistance remains critical to overcoming therapeutic limitations, emphasizing the importance of collaborative efforts in research and clinical practice to refine therapeutic approaches and improve survival rates for patients with metastatic melanoma involving the gastrointestinal tract. Future directions include optimizing combination therapies and leveraging precision medicine to address resistance and disease progression.
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Open AccessReview
The Role of Osimertinib in Stage I–II Non-Small-Cell Lung Cancer with Activating EGFR Mutation
by
Cesare Gridelli, Emanuela Nuccio and Francesca Casaluce
Targets 2025, 3(2), 20; https://doi.org/10.3390/targets3020020 - 11 Jun 2025
Cited by 1
Abstract
Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide with only approximately 30% of new diagnoses manifesting with localized stages IA–IIA. Osimertinib is a third-generation inhibitor of the epidermal growth factor receptor (EGFR), which is used for treating metastatic, locally
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Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide with only approximately 30% of new diagnoses manifesting with localized stages IA–IIA. Osimertinib is a third-generation inhibitor of the epidermal growth factor receptor (EGFR), which is used for treating metastatic, locally advanced, and early-stage NSCLC expressing common EGFR mutations. Two phase III clinical trials supported yresectable locally advanced disease, consisting of the ADAURA and LAURA studies, respectively. On the other hand, conflicting data on neoadjuvant efficacy led to the design of the ongoing Neo-ADAURA trial. In this review, we describe the pivotal trials that led to the approval of osimertinib use as an adjuvant treatment in radically resected NSCLC patients and as maintenance therapy after chemoradiotherapy. We also summarize the principal ongoing clinical trials in the neoadjuvant and adjuvant settings. Finally, we analyze several issues about the use of osimertinib in those different early settings while also depicting future perspectives and the potential evolution of treatment strategies.
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Anti-Inflammatory, Analgesic, and Anxiolytic Effects of Crude Extracts and Isolated Bioactive Fractional Compounds from Pouzolzia sanguinea
by
Md. Qamrul Ahsan, Rateep Nasim, Md. Talat Nasim and S. M. Shahinul Islam
Targets 2025, 3(2), 19; https://doi.org/10.3390/targets3020019 - 10 Jun 2025
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Pharmacological relevance: Ethnic people residing in the Chittagong Hill Tracts (CHTs) of Bangladesh use Pouzolzia sanguinea to alleviate flatulence, for menstruation, inflammation, insomnia, and analgesia. However, there is no scientific evidence regarding the bioactivity of these plants. Aim: This study aimed to isolate
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Pharmacological relevance: Ethnic people residing in the Chittagong Hill Tracts (CHTs) of Bangladesh use Pouzolzia sanguinea to alleviate flatulence, for menstruation, inflammation, insomnia, and analgesia. However, there is no scientific evidence regarding the bioactivity of these plants. Aim: This study aimed to isolate bioactive fractional compounds from Pouzolzia sanguinea (IFCPS) crude extract to assess the anti-inflammatory, analgesic, and anxiolytic activities. Materials and Methods: Preparative TLC-bioautography and silica gel two-stage column chromatography were used to isolate bioactive fractional compounds from P. sanguinea methanol crude extracts. The anti-inflammatory, analgesic, and anxiolytic activities of extracts and IFCPS were studied by inhibiting protein denaturation, acetic acid-induced writhing, Eddy’s hot plate, field cross, and hole cross methods. Results: The dried crude extract’s chemical analysis revealed alkaloids, flavonoids, terpenoids, saponins, vitamin C, and tannins. Nine single isolated fractional compounds (IFC1PS to IFC9PS) were isolated through TLC. Among these, IFC2PS exhibited (p ˂ 0.01) the most potent anti-inflammatory activity in the inhibition of protein denaturation studies (70.51%), which was slightly lower than acetyl salicylic acid (82.29%), at160 µg/mL. This inhibitory effect occurred in a dose-dependent manner. IFC2PS exhibited the most potent peripheral analgesic and moderate central analgesic effects compared to the standard. In contrast, IFC1PS showed moderate effects in both areas. IFC8PS showed superior anxiolytic activities compared to crude extracts and other IFCPS. Conclusions: Out of the nine fractional compounds isolated, the IFC2PS reduced pain and inflammation, whilst IFC8PS exhibited anxiolytic activities. This is the first comprehensive study demonstrating the anti-inflammatory, analgesic, and anxiolytic effects of crude extracts and isolated fractional compounds from the whole plant of P. sanguinea, which may have immediate experimental and clinical applications.
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