Targets, Volume 4, Issue 2 (June 2026) – 10 articles

Supportive care is essential during chemotherapy for head and neck cancer, yet the role of traditional Japanese medicine (kampo) remains unclear; therefore, we investigated whether Ninjin’yoeito (NYT) could reduce adverse events during cisplatin-based chemotherapy. We retrospectively analyzed 47 patients treated between June 2022 and June 2024, dividing them into an NYT group and a control group. Hematological toxicities, including decreases in white blood cells, neutrophils, hemoglobin, and platelets, as well as gastrointestinal disorders such as nausea, were evaluated. Compared with controls, patients receiving NYT showed significantly lower incidences of decreased white blood cell counts (p = 0.04), decreased hemoglobin levels (p = 0.03), and gastrointestinal disorders (p = 0.04). Trends toward reduced neutropenia and thrombocytopenia were also observed, although these did not reach statistical significance. These findings suggest that NYT may help mitigate hematological and gastrointestinal toxicities associated with cisplatin-based chemotherapy in patients with head and neck cancer. However, given the retrospective design and limited sample size, prospective studies are needed to confirm the efficacy and safety of NYT in this setting. Full article

Cerebral amyloid angiopathy (CAA) is a prevalent cerebral small vessel disease (CSVD) and prominent cause of vascular contributions to cognitive impairments and dementia (VCID). CAA is characterized by progressive accumulation of fibrillar amyloid β in cerebral vessel walls, leading to vascular wall degeneration, thrombotic occlusions, microbleeds, and perivascular inflammation causing cognitive deficits. Underlying mechanisms of CAA progression are poorly understood, and there exist no validated diagnostic biomarkers or therapeutic targets for CAA. Here, we performed proteomic mass spectrometry analysis of whole brain tissue and cerebral microvessel enriched fractions from the rTg-DI rat, a validated and well-characterized preclinical rat model of CAA, to identify potential targets and diagnostic markers related to vasculopathy progression in CAA. There were 92 increased and 104 decreased proteins identified in the rTg-DI whole brain samples, while 29 proteins were identified as increased in the enriched cerebral microvessel fractions. We identified several significant differentially expressed proteins in both sample types with commonly elevated proteins including HTRA1, APOE, APOD, CLU, MDK, and LAP3. This study also confirmed the differential expression of several proteins previously reported in isolated brain regions of rTg-DI rats, including ANXA3, APOD, APOE, CLU, CST3, CTSS, CTSD, CTSZ, GFAP, GSTA3, HTRA1, and ITGB2, with APOE, CLU, HTRA1, and GPC1 all reported in human CAA cases. We thus provide a “high-confidence” list of potential marker candidates from proteomic analysis in the rTg-DI rat model of capillary CAA type-1. Full article

Gambling disorder (GD) constitutes a worldwide social and economic burden and is associated with impaired functioning and reduced quality of life. GD shares important mechanistic substrates with obsessive–compulsive disorder (OCD), including dysfunction of cortico-striato-thalamo-cortical circuitry and dysregulation of serotonergic pathways involved in impulsivity, compulsivity, and impaired inhibitory control. On this basis, selective serotonin reuptake inhibitors (SSRIs), widely used in several psychiatric disorders, have been investigated as potential pharmacological treatments for GD. Evidence concerning fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram is heterogeneous and overall limited. Some early single-blind, randomized, and open-label studies have reported reductions in gambling urges, severity, and compulsive symptoms. However, larger and more rigorous placebo-controlled trials have frequently failed to demonstrate consistent superiority over placebo. Interpretation of these findings is further limited by small sample sizes, short observation periods, high dropout rates, heterogeneous outcome measures, and substantial placebo response. While SSRIs remain biologically plausible candidates for modulating the compulsive and impulsive dimensions of GD, current evidence does not support their routine use as first-line pharmacological treatment. Their role appears most justified in the presence of psychiatric comorbidity or within individualized, phenotype-oriented treatment strategies. Full article

Composed of a steroid nucleus, widely distributed in the animal and plant kingdoms, containing various hydroxyl and methyl groups, and a carboxyl side chain, bile acids (BAs) appear to be the result of an irreversible evolution in nature. BAs are involved in numerous vital processes, such as enterohepatic circulation, recognition and transport by various proteins, and their role as “clients” of the farnesoid X receptor, suggesting that they could be used as carriers, transporters, or Trojan horses to deliver a drug to its target. Pioneers of this approach include Ehrlich, Ho, and Kramer, who conceived of “magic bullet” concepts and designed what are now known as conjugated BAs or drug–BA complexes. This review focuses on articles that apply these concepts to the broad and complex field of cancer research. Most of the reviewed studies follow a common trajectory encompassing the design and synthesis of BA conjugates, the in vitro evaluation of their anticancer activity in various cell lines, and their subsequent in vivo assessment. More than 250 compounds have been taken into consideration. Full article

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