Targets

Intracranial mesenchymal tumors (IMTs) with FET::CREB fusion are rare mesenchymal neoplasms that rely on the confirmation of the molecular hallmark FET::CREB gene fusion for diagnosis. We report a case of a 53-year-old female presenting with neurocognitive decline and seizures. Neuroimaging demonstrated a heterogeneously enhancing solid-cystic lesion in the left frontal lobe. Gross total resection (GTR) of the tumor was achieved and the patient recovered to premorbid status. Definitive diagnosis was achieved via next-generation sequencing that identified an EWSR1 (exon 7)::CREM (exon 7) fusion transcript. A systematic literature review of 72 IMTs with FET::CREB-positive cases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Publications reporting confirmed FET::CREB fusion-positive IMTs, without restriction on year of publication, were included to analyze clinicopathological correlations and prognostic determinants. Mean age at diagnosis was 27.8 (±18.3). Patients who underwent GTR demonstrated a significantly lower rate of recurrence compared to those who underwent subtotal resection (STR) (p < 0.001), suggesting that extent of resection may be an important prognostic factor; however, causal inference is precluded by the observational nature of the data. Patients who received adjuvant therapy had a higher rate of recurrence (p = 0.043); however, this association is likely attributable to confounding by indication, as adjuvant treatment was predominantly administered to patients with subtotal resection or more aggressive disease. No causal inference regarding adjuvant therapy efficacy can be drawn from these data. Our study results corroborate that accurate diagnosis relies on molecular interrogation and the extent of resection appears to be an important prognostic factor for IMTs with FET::CREB fusion. Full article

CRISPR-based diagnostics integrated with nucleic acid pre-amplification have demonstrated profound potential for single-molecule detection. However, the pervasive risk of aerosol contamination during amplification significantly hinders their translation to point-of-care testing (POCT). Although amplification-free CRISPR diagnostics promise a streamlined “sample-to-answer” workflow, their development remains in the nascent stages due to the sluggish cleavage kinetics of natural Cas enzymes and the diffusion limitations of trace targets in homogeneous systems. This review systematically summarizes recent core technological advancements, including molecular engineering of CRISPR/Cas systems, novel signal transduction enhancement mechanisms, and digital detection methodologies based on spatial confinement effects. Furthermore, addressing the “matrix effect” that often compromises analytical sensitivity in clinical scenarios, we highlight advanced pre-treatment strategies for complex biological samples. Finally, we propose that the future of POCT relies on the synergy of multiplexed detection, AI-assisted analysis, and microfluidic integration to ultimately bridge the gap between laboratory innovation and clinical application. Full article

Accurate analysis of prostate cancer (PC)-related biomarkers requires sensing platforms capable of sensitive and multiplex detection in complex biological environments. Herein, we propose a signal-on electrochemical aptamer-based sensor (E-AB) for the simultaneous detection of L-lactate (L-Lac) and prostate-specific antigen (PSA). To maximize analytical performance, two Lac aptamer sensing configurations, single-stranded (ssLac201) and double-stranded (dsLac201), were constructed and comparatively evaluated. The dsLac201 structure displayed more effective background suppression and enhanced target induced signal response. Under optimized conditions, the dsLac201-based sensor exhibited a wide linear range from 500 nM to 10 mM for L-Lac, with a low detection limit of 157 nM and high selectivity. Based on this optimized design, a dual-aptamer electrochemical platform was further engineered through programmable nucleic acid assembly, enabling simultaneous detection of L-Lac and PSA via dual-input signal integration. The dual-target sensor showed broad analytical ranges for both biomarkers (L-Lac: 500 nM–10 mM; PSA: 10 pg mL⁻¹–500 ng mL⁻¹) and retained promising performance in serum samples. This work demonstrates a simple and versatile strategy for multiplex electrochemical biosensing and provides a promising platform for PC-related biomarker monitoring and clinical biomedical analysis. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, frequently arising from chronic inflammatory states such as metabolic dysfunction-associated steatotic liver disease and cirrhosis. While extensive epidemiological data demonstrate a strong, dose-dependent inverse association between habitual coffee consumption and HCC incidence, the underlying molecular causality remains incompletely understood. In this comprehensive review, we elucidate the “Coffee Paradox” through the lens of nutriepigenomics. We demonstrate how coffee-derived bioactives—specifically chlorogenic acids, diterpenes, and microbially derived short-chain fatty acids—function as a coordinated epigenetic defense system. These compounds actively inhibit DNA methyltransferases, serve as endogenous histone deacetylase inhibitors via the gut–liver axis, and induce post-transcriptional, tumor-suppressive microRNA networks to halt oncogenic progression. However, to provide a critical and balanced perspective, we also address significant translational challenges. We evaluate conflicting null associations from recent Mendelian randomization studies and highlight the profound variability introduced by specific brewing methods, roasting profiles, and individual pharmacogenomics (e.g., CYP1A2 polymorphisms). Finally, we outline the future of precision hepatology, emphasizing the critical transition from observational epidemiology to clinical application via the utilization of circulating exosomal microRNAs as dynamic liquid biopsies and the development of standardized epi-nutraceuticals. Ultimately, this multi-layered epigenetic framework provides a robust foundation for integrating targeted dietary interventions into the primary prevention of HCC. Full article

Hepatic hemangiomas are the most common benign liver tumors and are typically small and asymptomatic; however, pedunculated and exophytic variants are extremely rare and may mimic extrahepatic lesions on imaging, posing a potential diagnostic challenge. The aim of this study was to describe the multimodal imaging features of a pedunculated hepatic hemangioma arising from the left triangular ligament and to review the available literature with particular attention to MRI findings and diagnostic considerations. A 52-year-old man underwent contrast-enhanced thoracoabdominal CT for unrelated symptoms, which incidentally revealed a pedunculated hepatic lesion. Further evaluation was performed with multiparametric MRI at 1.5T, including diffusion-weighted imaging and dynamic contrast-enhanced sequences. A review of the English-language literature published up to 2025 focusing on pedunculated and exophytic hepatic hemangiomas was also conducted. CT and MRI demonstrated imaging features consistent with hepatic hemangioma, including peripheral nodular enhancement with progressive centripetal fill-in and marked T2 hyperintensity. Multiplanar MRI depicted a thin vascular pedicle connecting the lesion to the hepatic capsule, supporting its hepatic origin. Fewer than approximately 30 well-documented cases have been reported in the English literature. Recognition of these imaging findings may facilitate correct diagnosis and help avoid unnecessary invasive procedures. Full article

Aging is a complex biological process characterized by progressive loss of cellular homeostasis, impaired regenerative capacity, and accumulation of senescent cells that collectively predispose tissues to disease. Traditional two-dimensional culture systems and animal models have provided valuable insights but fail to fully recapitulate the spatial organization, cellular heterogeneity, and microenvironmental cues of aging human tissues. Organoid technology—three-dimensional self-organizing structures derived from adult stem cells or pluripotent stem cells has emerged as a transformative platform to model aging in vitro. These mini-tissues retain the architecture, signaling dynamics, and lineage hierarchy of native organs, making them powerful systems to interrogate age-associated cellular phenotypes, DNA damage responses, and senescence programs. This review discusses how organoid models are advancing our understanding of aging biology across multiple organ systems, from the intestines and liver to the brain and lung. We highlighted key molecular pathways driving cellular senescence within organoids—including p16INK4a/p21CIP1 signaling, SASP activation, mitochondrial dysfunction, and epigenetic drift—and how these can be targeted to restore tissue homeostasis. We further discussed how organoids derived from aged tissues, induced pluripotent stem cells, and engineered oncogene systems reveal new therapeutic opportunities to modulate senescence in age-related disorders, cancer, and regenerative medicine. Finally, we discussed emerging integrative tools such as organoid co-cultures, single-cell omics, and senolytics drug screening that are expanding the potential of organoids as translational platforms for anti-aging and disease intervention. Full article

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

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. Full article

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. Full article