Targets, Volume 4, Issue 1 (March 2026) – 11 articles

Rare earth elements (REEs), located in the IIIB group of the periodic table, can be detected in very small quantities by sensitive detection techniques. REE labeling technologies utilize fluorescent labeling, magnetic labeling, atomic fluorescence labeling, fluorescence resonance energy transfer (FRET) labeling and radiolabeling. Widely used immunoassays related to REE-labeled technologies include time-resolved fluorescence immunofluorescence assay (TRFIA), inductively coupled plasma–mass spectrometry (ICP–MS)-based immunoassays, mass spectrometry flow-through (CyTOF), and upconversion nanoparticles (UCNPs). REE-labeled immunoassays have been widely used in various fields, such as biological analysis, biomarker detection and analysis of food detection techniques, as these assays can use low quantities of biological tissue, exhibit stability, can label materials, lack radioactivity and show multidetection capability. To provide researchers with a deeper understanding of the immunoassay technique used to label rare earth elements, this paper reviews its labeling principle, detection technology, and application. Full article

The epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are key members of the receptor tyrosine kinase family. Under normal physiological conditions, they play crucial roles in regulating cellular homeostasis and development, including cell differentiation, proliferation, and survival. However, when dysregulated due to mutation, amplification, or overexpression, these receptors become potent drivers of tumorigenesis, especially in breast cancer (BC). BC, being the second most prevalent cancer globally, remains a major contributor to female mortality. The EGFR and HER2 overexpression are present in nearly 15–30% of all BC cases and are a hallmark of aggressive BC and drug resistance, correlating with poor prognosis. Over the years, multiple tyrosine kinase inhibitors (TKIs) have been developed, showing promising responses against previously limited treatment options. This review focuses on strategies for designing dual EGFR-HER2 inhibitors for the treatment of BC and on insights into the development of new dual inhibitors. Full article

Cancer cachexia is a multifactorial metabolic syndrome that profoundly impairs treatment tolerance and prognosis; however, how tumor-intrinsic transcriptional programs contribute to cachexia induction and shape responses to chemotherapeutic stress remains poorly understood. In this study, we analyzed a paired human duodenal neuroendocrine carcinoma cell-line model consisting of the non-cachexia-inducing parental line TCC-NECT-2 and its cachexia-inducing derivative AkuNEC. Bulk RNA sequencing was performed under baseline conditions and after doxorubicin treatment (10 μM, 24 h), and transcriptomic differences were assessed using log2 fold-change–based analyses to characterize baseline reprogramming, drug-induced responses, and differential stress adaptation. Despite comparable morphology and similar levels of doxorubicin-induced acute cytotoxicity, AkuNEC cells exhibited extensive baseline transcriptional reprogramming relative to TCC-NECT-2, including coordinated upregulation of inflammatory, secretory, and metabolic regulators previously implicated in cancer cachexia, together with suppression of structural and homeostatic programs. Following doxorubicin exposure, AkuNEC cells showed a distinct transcriptional response characterized by selective reorganization of proliferation-, metabolism-, and stress-related pathways, indicating enhanced transcriptional plasticity rather than uniform stress suppression. Differential response analyses further revealed preferential induction of genes involved in cell cycle control, DNA replication, and metabolic adaptation in AkuNEC under chemotherapeutic stress. These findings indicate that cachexia-inducing capacity is embedded within tumor-intrinsic transcriptional states and is amplified by stress-induced plasticity, supporting a network-level model of cancer cachexia that links systemic host effects with tumor adaptation to therapy. The TCC-NECT-2/AkuNEC model provides a tractable framework for dissecting these tumor-intrinsic mechanisms and their relevance to cachexia-associated cancer biology. Full article

Arachidonic acid 5-lipoxygenase (ALOX5), an enzyme critical for lipid mediator synthesis, demonstrates significant upregulation in clinically distinct disease states. Current research identifies its aberrant activity in neurodegenerative pathologies (e.g., Parkinson’s disease), solid tumors, hematological cancers, metabolic dysregulation linked to diabetic nephropathy, and vascular remodeling in hypertension and coronary artery disease. These findings collectively implicate ALOX5 as a multifunctional driver of chronic inflammation and tissue damage across organ systems. Despite the significant clinical significance of ALOX5, developing effective inhibitors for this target remains challenging, with most candidates still undergoing clinical evaluation. This study employs a multi-stage computational approach to identify novel ALOX5 inhibitors with strong drug-like properties. By compiling compounds with documented ALOX5 inhibitory activity and IC50 values from PubChem, ChEMBL, and MedChemExpress databases, we established a ligand-based pharmacophore model to virtually screen terpenoid derivatives. The selection of terpenoid compounds for virtual screening is primarily due to their dual role as natural products exhibiting significant structural diversity alongside a broad spectrum of known biological activities. This provides an ideal starting point for the efficient discovery of structurally novel lead compounds with drug potential, while also being well-suited for structure-based computational evaluation. Two lead compounds (29835 and 38032) were identified through ADMET property prediction and scaffold modification-guided optimization. Molecular docking analysis revealed superior binding affinities for these candidates (−8.31 and −10.26 kcal/mol, respectively) compared to Zileuton (−7.39 kcal/mol), indicating stable and favorable interactions within the target protein’s active site. The binding stability of these complexes was further confirmed by 100 ns molecular dynamics simulations, which demonstrated sustained structural integrity of the protein–ligand systems. Collectively, computational findings suggest these compounds as promising ALOX5 inhibitors. However, given the theoretical framework of this work, subsequent experimental validation via in vitro and in vivo pharmacological assays is imperative to verify their therapeutic potential. Full article

Retinoblastoma is a prevalent pediatric malignant tumour of the retina, primarily caused by biallelic inactivation of the RB1 gene or, less commonly, amplification of the MYCN oncogene. It has a global incidence of approximately 1 in 15,000–18,000 live births and predominantly affects children under five years of age. Trefoil factor 1 (TFF1) is a small, secreted peptide from the trefoil family, mainly expressed in the gastrointestinal mucosa, where it plays an essential role in mucosal protection, repair, and cellular differentiation. Beyond its physiological functions, aberrant TFF1 expression has been implicated in tumour progression and oncogenic signalling across several cancers. TFF1 is not expressed in healthy human retina but is significantly expressed in retinoblastoma tissues, with higher levels correlating with advanced disease stage, high-risk histopathologic features (HRPFs) and metastasis, poor differentiation, and unfavourable prognosis, suggesting a potential role of TFF1 in the pathogenesis and progression of retinoblastoma. Furthermore, in addition to tumour biopsy, its detection in the aqueous humour indicates its potential utility as a non-invasive biomarker for tumour activity and treatment monitoring. Although the precise molecular mechanisms underlying TFF1’s function in retinoblastoma remain unclear, evidence suggests that it may modulate tumour aggressiveness through effects on cell proliferation, apoptosis, and tumour microenvironmental signalling, supporting its promise as a prognostic biomarker and potential therapeutic target. This review consolidates the current advances in the role of TFF1 in retinoblastoma and critically examines its emerging significance as a potential clinical biomarker, molecular mediator, and novel therapeutic target for retinoblastoma. Full article

Single-cell transcriptomics has redefined our understanding of cancer by exposing the complexity of tumor ecosystems and their therapeutic vulnerabilities. scRNA-seq studies have identified lineage hierarchies, immune evasion programs, and resistance-associated states across solid and liquid tumors, informing biomarker development and drug discovery. Advanced computational frameworks integrate these data with longitudinal profiling, RNA velocity, and network diffusion to prioritize targets and predict therapeutic response. Emerging multi-omics approaches further expand the scope of precision oncology by linking genetic alterations, protein-level markers, and spatial context to functional states. This narrative review aims to synthesize current applications of single-cell transcriptomics for target discovery, highlight computational frameworks that translate high-dimensional data into actionable insights, and explore how multi-omics integration is shaping future directions. By bridging molecular complexity with target prioritization, these approaches hold promise for translating single-cell insights into clinically actionable biomarkers and therapeutic strategies for personalized cancer treatment and rational drug development. Full article

Zinc homeostasis is fundamental to metabolic health, orchestrated by the coordinated actions of two major zinc transporter families: ZIP (Zrt- and Irt-like proteins) and ZnT (zinc transporters). ZIP transporters facilitate zinc influx into the cytosol from the extracellular space or from the lumen of intracellular organelles, whereas ZnT transporters control zinc efflux from the cytosol to the extracellular space or facilitate its sequestration into intracellular vesicles and organelles, concurrently harboring the meticulous intracellular zinc homeostasis. This equilibrium is essential for all critical functions like cellular response, metabolic control, and immune pathway alteration. Disruption of this homeostasis is a driver of different pathological alterations like metabolic inflammation, a chronic low-grade inflammatory state underlying obesity; type 2 diabetes; and nonalcoholic fatty liver disease. Recent studies revealed that ZIP and ZnT transporters dynamically regulate metabolic and inflammatory cues, with their tissue-specific expression varying by tissue and acclimating to different physiological and pathological conditions. Recent advanced research in molecular and genetic understanding has helped to deepen our knowledge of the interplay of activity between ZIP and ZnT transporters and their crosstalk in metabolic tissues, underscoring the potential therapeutic prospect for restoring zinc balance and ameliorating metabolic inflammation. This review provides a comprehensive overview that covers the function, regulation, and interactive crosstalk of ZIP and ZnT zinc transporters in metabolic tissues and their pathological conditions. Full article

The indole scaffold represents a privileged structural motif in medicinal chemistry, celebrated for its remarkable chemical versatility, biological ubiquity, and clinical relevance. This review provides a comprehensive analysis of the recent research on the indole nucleus, emphasizing its physicochemical properties, reactivity patterns, and capacity to interact with a wide array of biological targets. Found in key endogenous compounds such as serotonin and melatonin, indole serves as a cornerstone in neurochemical signaling, circadian regulation, and chrono-metabolic homeostasis. Beyond its physiological roles, synthetic indole derivatives have shown extensive therapeutic potential across diverse domains, including oncology, infectious diseases, neurodegenerative disorders, immunomodulation, and metabolic syndromes. The review explores structure–activity relationships (SAR), pharmacokinetics, and the molecular mechanisms by which indole-based compounds exert their tremendous effects, that are ranging from enzyme inhibition to receptor modulation. Special focus is given to current clinical applications and emerging strategies for enhancing drug specificity, bioavailability, and safety through indolic frameworks. Additionally, we highlight the translational potential of indole-containing molecules in personalized medicine, underscoring opportunities for future drug discovery. By integrating insights from medicinal chemistry, biochemistry, pharmacology, and clinical science, this review affirms the indole ring’s enduring value as a central scaffold in therapeutic innovation. Full article

Head and neck cancer (HNC) patients frequently experience alterations in the oral environment following radiotherapy, including xerostomia and impaired mucosal integrity, which may favour fungal overgrowth. This study aimed to characterise oral Candida colonisation in radiotherapy-treated HNC patients and compare it with that of healthy individuals. Unstimulated saliva samples from 61 HNC patients and 100 controls were cultured on chromogenic agar, and isolates were identified using API 20C AUX or MALDI-TOF. Salivary flow was measured to quantify xerostomia. A representative subset of isolates (10 per group) underwent antifungal susceptibility testing by disk diffusion according to CLSI/EUCAST criteria. Candida colonisation was significantly higher in HNC patients than in controls (64.6% vs. 20%, p < 0.001), with greater species diversity and increased detection of non-albicans yeasts, including C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei. All HNC patients exhibited reduced salivary flow. Azole resistance was more frequent among HNC isolates (26%) than among controls (10%), whereas all isolates remained susceptible to amphotericin B and nystatin. These findings indicate that radiotherapy-associated xerostomia substantially alters the oral mycobiota and underscore the importance of routine species-level identification and antifungal susceptibility testing in HNC patients to guide clinical decision-making. Full article

Background/Objectives: This pilot study investigates the feasibility of using patient-derived microtumors (PDMs) to assess chemotherapy response in epithelial ovarian cancer. Methods: Fresh tissue from 10 patients was used to develop PDMs, which were then tested against carboplatin/paclitaxel, carboplatin/docetaxel, and carboplatin/pegylated liposomal doxorubicin (PLD). Of the 10 PDMs, 3 were obtained from primary debulking surgery (PDS), and 7 were obtained at the time of interval debulking surgery following neoadjuvant chemotherapy. Results: When looking at PDMs derived from tissue collected at the time of PDS, we found that 100% of PDMs demonstrated a full response to carboplatin/PLD, while 30% showed a full response to all regimens, all of which were derived from high-grade serous carcinoma during PDS. The remaining PDMs showed moderate responses to carbo/taxol and carbo/doce. Conclusions: This study suggests that PDMs can be used to assess the efficacy of chemotherapy regimens, as a hypothesis-generating step toward future predictive validation. Full article

Acetylcholinesterase (AChE) is an important molecular target in the development of insecticides, but due to also being found in the human body, it is necessary to characterize the inhibitory profile of compounds to achieve selectivity. In this study, we employed molecular modeling and 3D-QSAR approaches to identify novel compounds that inhibit AChE1 in Bemisia tabaci, a common agricultural pest in tropical and subtropical crops. We conducted molecular docking simulations and quantitative structure–activity relationship analysis (QSAR) to identify compounds with potential inhibitory activity and to develop a predictive model for the activity of these new compounds. The validated model demonstrated remarkable predictive performance. Using the model, we screened a library of novel moieties in favorable regions of the most active molecules in the dataset and identified promising candidates, including FS168. We performed molecular dynamics simulations with FS168 bound to the AChE1 of B. tabaci and observed stabilization and interaction with important catalytic amino acids, indicating a potential inhibition mechanism. Our results showcase the potential of combining molecular modeling and 3D-QSAR approaches for discovering new potential AChE1 inhibitors in Bemisia tabaci as selective agrochemicals. Full article