Ann Med. 2025 Dec;57(1):2478316. doi: 10.1080/07853890.2025.2478316. Epub 2025 Mar 26.

ABSTRACT

BACKGROUND: Isoniazid is primarily metabolized by the arylamine N-acetyltransferase 2 (NAT2) enzyme. Single nucleotide polymorphisms (SNPs) in the NAT2 gene could classify an individual into three distinct phenotypes: rapid, intermediate and slow acetylators. NAT2 SNPs and the slow acetylator phenotype have been implicated as risk factors for the development of antitubercular drug-induced liver injury (AT-DILI) in several tuberculosis (TB) populations.

PATIENTS AND METHODS: We conducted a prospective observational study to characterize and compare the NAT2 SNPs, genotypes and phenotypes among patients with TB and AT-DILI from the Southern and Western regions of India. The NAT2 pharmacogenomic profile of patients from these regions was compared with the reports from several geographically diverse TB populations and participants of different genetic ancestries extracted from literature reviews and the 'All of Us' Research Program database, respectively.

RESULTS: The TB patients of Southern and Western regions of India and several other geographically closer regions exhibited near similar NAT2 MAF characteristics. However significant heterogeneity in NAT2 SNPs was observed within and between countries among AT-DILI populations and the participants of different genetic ancestry from the 'All of Us' Research Program database. The MAF of the NAT2 SNPs rs1041983, rs1801280, rs1799929, rs1799930 and rs1208 of the TB patients from Southern and Western Indian Sites were in near range to that of the South Asian genetic ancestry of 'All of Us' Research Program database. About one-third of the total TB patients from the Southern and Western regions of India were NAT2 slow acetylators, among whom a relatively higher proportion experienced AT-DILI.

CONCLUSION: Further studies exploring the risk of NAT2 SNPs in different AT-DILI patients with larger sample sizes and a population-specific approach are required to establish a policy for NAT2 genotyping as a pre-emptive biomarker for AT-DILI monitoring for personalized isoniazid therapy in clinics.

PMID:40138446 | DOI:10.1080/07853890.2025.2478316

Neurochem Res. 2025 Mar 26;50(2):127. doi: 10.1007/s11064-025-04382-2.

NO ABSTRACT

PMID:40138046 | DOI:10.1007/s11064-025-04382-2

BMJ Open Respir Res. 2025 Mar 26;12(1):e003044. doi: 10.1136/bmjresp-2024-003044.

ABSTRACT

BACKGROUND: Respiratory virus infections are a major cause of morbidity in early life. During the SARS-CoV-2 pandemic, non-pharmaceutical interventions (NPIs) lead to worldwide changes in respiratory virus epidemiology. However, evidence regarding virus circulation in the outpatient setting remains largely unknown. The aim of this study is to longitudinally assess respiratory viruses in healthy infants before and during the SARS-CoV-2 pandemic in Switzerland.

METHODS: In this prospective observational birth cohort study, we followed 34 infants throughout the first year of life before and during the SARS-CoV-2 pandemic. We analysed 648 biweekly nasal swabs for nine different respiratory viruses by Multiplex-PCR and assessed respiratory symptoms, COVID-19 infections of family members and childcare status in weekly interviews. 712 nasal swabs from 32 infants analysed before the pandemic and published previously served as control group.

RESULTS: During the period with strict NPIs (pandemic I), most common respiratory viruses were not detected, with a rebound (driven by Adenovirus and Parainfluenza virus) after most NPIs were relaxed (pandemic II): prepandemic: 27%, pandemic I: 19%, pandemic II: 33%; historic: 36% of collected swabs per period, p<0.001. Human rhinovirus (HRV) prevalence persisted during NPIs presence, mainly in the form of asymptomatic HRV detection: prepandemic=24%, pandemic I=19%, pandemic II=25%, historic: 25%, p=0.3. SARS-CoV-2 detection (asymptomatic and symptomatic) was low, and only present after NPIs were relaxed: pandemic II=2.4%. No severe COVID-19 infections were reported.

DISCUSSION: In our cohort, infants did not contribute largely to spread of SARS-CoV-2. The role of persisting asymptomatic HRV prevalence is still unclear, but it might help to maintain population immunity to prevent more severe infections. Our results underscore the importance of capturing asymptomatic viruses via longitudinal community-based data assessment to better understand virus transmission.

PMID:40139841 | DOI:10.1136/bmjresp-2024-003044

Biochemistry. 2025 Mar 26. doi: 10.1021/acs.biochem.4c00780. Online ahead of print.

ABSTRACT

Lumacaftor and Ivacaftor are two FDA-approved medications currently used to treat cystic fibrosis (CF), a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride ion channel located in epithelial cell membranes; however, the detailed mechanism(s) of their action remains to be elucidated. Both drugs, termed modulators, bind CFTR at a protein-lipid interface, yet Lumacaftor acts at the endoplasmic reticulum (ER), while Ivacaftor acts at the plasma membrane (PM). A major difference among biological membranes is their level of cholesterol (viz., the ER, 5% cholesterol; the Golgi apparatus, 12.5%; and the PM, 30%). Therefore, we investigated the ability of each molecule to interact with membranes of the corresponding cholesterol content to determine if lipid cholesterol content provides a physical basis for their observed localized activity. Using differential scanning calorimetry and a terbium-based liposome disruption assay, we show that both Lumacaftor (a corrector) and Ivacaftor (a potentiator) penetrate/diffuse through membranes containing high cholesterol concentrations, such as in Golgi and the PM. The results further suggest that (1) Lumacaftor resides within membranes containing 5% cholesterol, supporting the proposition that Lumacaftor acts as a corrector of the CFTR channel at the ER level where the nascent protein is in its initial folding stage; and (2) Ivacaftor is well-suited to penetrate the PM and reach its binding pocket on CFTR. Our findings provide evidence that membrane cholesterol levels significantly modulate CFTR corrector/potentiator activity and consequently may affect sensitivity to clinical therapeutics in CF patients.

PMID:40138627 | DOI:10.1021/acs.biochem.4c00780

Pathogens. 2025 Mar 12;14(3):271. doi: 10.3390/pathogens14030271.

ABSTRACT

The Achromobacter genus comprises 22 species and various genogroups. Some species with higher virulence or antibiotic resistance are more likely to cause chronic infections in people with cystic fibrosis (CF). Current identification methods often fail to accurately distinguish between the species or result in misidentifications due to biochemical similarities. This study aims to develop an accurate qPCR protocol for species-level identification that is applicable in clinical diagnostic laboratories. Whole-genome sequencing of clinical isolates from different Achromobacter species identified species-specific single-nucleotide polymorphisms (SNPs) in two 16S gene regions. Based on these SNPs, two sets of primers and qPCR probes were designed to generate unique identification profiles. Thermal profiles were optimized, and qPCR was performed on serial bacterial DNA dilutions to determine the detection limit (LOD). Four probes successfully identified three species: A. xylosoxidans, A. dolens, and A. insuavis. Two additional probes were designed for novel genotypes unrelated to publicly available sequences. The LOD ranged from 0.005 pg/µL to 1 pg/µL. Combined probes achieved 100% sensitivity, with specificity ranging from 97.95% to 100%. This qPCR protocol enables accurate species identification, overcoming the limitations of current methods, and represents a reliable tool for clinical diagnostics.

PMID:40137756 | DOI:10.3390/pathogens14030271

Cell Mol Gastroenterol Hepatol. 2025 Mar 24:101505. doi: 10.1016/j.jcmgh.2025.101505. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The incidence of Barrett esophagus (BE) and Gastroesophageal Adenocarcinoma (GEAC) correlates with obesity and a diet rich in fat. Bile acids (BA) support fat digestion and undergo microbial metabolism in the gut. The farnesoid X receptor (FXR) is an important modulator of the BA homeostasis. When activated, FXR can inhibit cancer-related processes and thus, it is an appealing therapeutic target. Here, we assess the effect of diet on the microbiota-BA axis and evaluate the role of FXR in disease progression.

METHODS: L2-IL1B mice (mouse model of BE and GEAC) under different diets, and L2-IL1B-FXR KO-mice were characterized. L2-IL1B-derived organoids were exposed to different BAs and to the FXR agonist obeticholic acid, OCA. The BA profile in serum and stool of healthy controls, BE- and GEAC-patients was assessed.

RESULTS: Here we show that high fat diet accelerated tumorigenesis in L2-IL1B mice while increasing BA levels and altering the composition of the gut microbiota. While upregulated in BE, expression of FXR was downregulated in GEAC in mice and humans. In L2-IL1B mice, FXR knockout enhanced the dysplastic phenotype and increased Lgr5 progenitor cell numbers. Treatment of murine BE organoids and L2-IL1B mice with OCA notably ameliorated the phenotype.

CONCLUSION: GEAC carcinogenesis appears to be partially driven via loss or inhibition of FXR on progenitor cells at the gastroesophageal junction. Considering that the resulting aggravation in the phenotype could be reversed with OCA treatment, we suggest that FXR agonists have great potential as a preventive strategy against GEAC progression.

PMID:40139565 | DOI:10.1016/j.jcmgh.2025.101505

Stem Cells Transl Med. 2025 Mar 18;14(3):szae099. doi: 10.1093/stcltm/szae099.

ABSTRACT

Many electronic cigarettes (ECs) contain high concentrations of menthol. The effect of menthol on human embryos in pregnant women who vape is not well understood. Human embryonic stem cells (hESCs) (an epiblast model) were used to test the hypothesis that 6.4-640 nM and 19.2-192 µM menthol, which activates TRP (transient-receptor-potential) channels, alters calcium homeostasis in embryos and adversely affects processes that are critical to gastrulation. Micromolar concentrations of menthol inhibited mitochondrial reductase activity in hESCs, an effect that was blocked by TRPA1 and TRPM8 inhibitors. Pulsatile exposure to menthol elevated intracellular calcium primarily by activating TRPA1 channels at nanomolar concentrations and TRPM8 channels at µM concentrations. nM menthol significantly inhibited colony growth by activating TRPA1 channels, while both TRPA1 and TRPM8 were activated by µM menthol. Inhibition of colony growth was attributed to cell death induced by menthol activation of TRPA1 and TRPM8 channels. nM menthol altered colony phenotype by increasing the major/minor axis ratio via TRPA1 and TRPM8 channels. Both nM and µM menthol induced alterations in hESC colony motility, an effect that was blocked only by the TRPM8 inhibitor. The menthol-induced increase in intracellular calcium adversely influenced growth, death, and migration, processes that are critical in gastrulation. Menthol concentrations that reach embryos in women who vape are high enough to activate TRPA1 and TRPM8 channels and perturbed calcium homeostasis. Pregnant women who vape likely expose their embryos to menthol concentrations that are harmful. These data could help prevent birth defects or embryo/fetal death.

PMID:40139559 | DOI:10.1093/stcltm/szae099

J Dairy Sci. 2025 Mar 24:S0022-0302(25)00171-7. doi: 10.3168/jds.2024-26011. Online ahead of print.

ABSTRACT

Improving calf health on dairy farms contributes to animal welfare and business productivity gains. In recent years, traditional genetic evaluations have broadened to include cow health traits that have economic importance. Calf health is a new frontier to explore but new traits require sufficient data to be effectively evaluated. Researchers who work in countries without obligatory record keeping systems, commonly promote the need to significantly improve record keeping practices to enable research, benchmarking, and genetic evaluation, as is the case in Australia. The aim of this study was to estimate variance components for novel calf traits using a data set that was co-designed with farmers and included calf identity, calving ease, health records and genotypes. Almost 20,000 calf records from over 50 farms located throughout Australia were collected between 2020 and 2023. In Holstein calves, the mean ± SE prevalence of preweaning mortality (PWM) and scours, were 0.020 ± 0.001 and 0.059 ± 0.002, respectively. A newly defined and subjectively scored trait called Calf Vitality (vitality) was co-developed with farmers, where 21% of calves were classed in the top category of ripper/vigorous, while 54% were good or average, 6% were duds and 19% of scored calves died. Univariate linear models that included a genomic relationship matrix were used to estimate variance components for diseases and vitality, where heritability values were between 1% and 11% in Holsteins depending on the trait. The models included herd-year-season (HYS), sex, parity group and calving ease (Holstein only) as fixed effects and these were found to be significant (P < 0.05 to 0.001) for most breed and trait combinations. The estimated reliability of EBVs ranged between 0.2 and 0.3. In Australia, Holsteins are more numerous than the Jersey breed, and so despite efforts to compile an appropriate data set, the disease prevalence and record numbers were too low to report genetic variance for calf health traits in the Jersey breed. Approximate genetic correlations with other calf health traits such as stillbirth (SB) and PWM were modest but favorable. There were few significant correlations with lactating cow traits (such as survival, somatic cell count and likeability) and national selection indexes that are routinely evaluated in Australia and those that were significant were in a favorable direction.

PMID:40139346 | DOI:10.3168/jds.2024-26011

Food Chem. 2025 Mar 19;480:143966. doi: 10.1016/j.foodchem.2025.143966. Online ahead of print.

ABSTRACT

Consumers' interest in healthy and sustainable food of superior organoleptic quality has contributed to an increased market of mildly processed chilled NFC orange juices, preserved by methods such as high pressure processing (HPP) and pulsed electric fields (PEF). To protect consumers from food fraud, analytical methods to differentiate such juices from thermally pasteurized juices are required. To screen for appropriate candidate markers, we applied a complementary non-targeted volatilomics and sensomics approach resulting in a total of 58 candidate markers, among which 20 were quantitated and nine were statistically confirmed. Extension of the quantitations to stored and doubly-treated juices finally resulted in (S)-carvone and vanillin as promising candidate markers. In combination, the two compounds allowed to distinguish the HPP-treated juice from thermally treated juices and even was able to identify an HPP-treated juice that had received an additional thermal pasteurization.

PMID:40138831 | DOI:10.1016/j.foodchem.2025.143966

Sci Adv. 2025 Mar 28;11(13):eads6021. doi: 10.1126/sciadv.ads6021. Epub 2025 Mar 26.

ABSTRACT

Emerging evidence has shown that epigenetic regulation plays a fundamental role in cancer metastasis, the major cause of cancer-related deaths. Here, we conducted an in vivo screen for vulnerabilities of brain metastasis and identified N-acetyltransferase 10 (NAT10) as a driver of brain metastasis. Knockdown of NAT10 restrains cancer cell proliferation and migration in vitro and tumor growth and brain metastasis in vivo. The poorly characterized RNA helicase domain of NAT10 is critical for cell growth in vitro, while both RNA helicase and NAT domains are essential for primary tumor growth and brain metastasis in vivo. Mechanically, NAT10 promotes the expression of 3-phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1), two enzymes for serine biosynthesis implicated in brain metastasis. Silencing PHGDH or PSAT1 in metastatic breast cancer cells inhibits their growth in the serine/glycine-limited condition, phenocopying the effects of NAT10 depletion. These findings establish NAT10 as a key regulator of brain metastasis and nominate NAT10 as a target for treating metastasis.

PMID:40138393 | DOI:10.1126/sciadv.ads6021

STAR Protoc. 2025 Mar 24;6(2):103714. doi: 10.1016/j.xpro.2025.103714. Online ahead of print.

ABSTRACT

A reproducible study system is essential for understanding the role of microbes in human skin health and disease. We present a protocol for constructing a synthetic microbial community (SkinCom) of nine strains dominant to native human skin microbiome. We describe steps for computing growth metrics, constructing communities, and extracting DNA and library preparation for shotgun sequencing. We detail steps for data preprocessing and analysis of community samples. We illustrate SkinCom's application with an epicutaneous murine model and downstream multiomic analysis. For complete details on the use and execution of this protocol, please refer to Lekbua et al.1.

PMID:40138316 | DOI:10.1016/j.xpro.2025.103714

PLoS One. 2025 Mar 26;20(3):e0320377. doi: 10.1371/journal.pone.0320377. eCollection 2025.

ABSTRACT

Decisions where an individual lays their eggs are important, as the choice may affect their offspring's survival and lifetime reproductive success. Information produced by conspecifics can potentially be useful in making decisions as this "social information" may provide an energetically cheaper means of assessing oviposition site suitability rather than acquiring it personally. However, as not all public information may be equally beneficial, cues produced by kin may be especially valuable as they might signal suitable microenvironments, and are associated with other fitness advantages resulting from improved foraging success and/or a decreased risk of competition/cannibalism compared to sites where unrelated conspecifics are located. Using the fruit fly, Drosophila melanogaster, we explored whether public information use is associated with kin-based egg-laying decisions. Kinship is potentially recognized in several ways, including environmentally-associated proxy cues, so we explored whether there were biases in how focal females interacted with cues from conspecifics that differed in both genetic relatedness, and environmental "familiarity." In a series of inter-connected assays, we examined the behaviour of focal females that interacted with a choice of potential egg-laying substrates that differed in the manner of their prior conspecific exposure, and counted the offspring that eclosed from these different substrates. Sites that had exhibited cues produced by conspecific demonstrators were visited more, and yielded more focal offspring compared to unexposed substrates. Furthermore, patterns of bias in offspring production were consistent with ovipositing females exhibiting sensitivity to the kinship status of the prior substrate's occupants. The basis of the kinship categorization by ovipositing females appears to be based on phenotypes that reflect true genetic relatedness, but the nature of the social information can be affected by other factors. These results further highlight the potential usefulness of D. melanogaster as a model to understand the evolution of social behaviour in the expression of decision-making.

PMID:40138267 | DOI:10.1371/journal.pone.0320377

Acta Neurol Belg. 2025 Mar 26. doi: 10.1007/s13760-025-02770-7. Online ahead of print.

NO ABSTRACT

PMID:40138160 | DOI:10.1007/s13760-025-02770-7

Cell Tissue Res. 2025 Mar 26. doi: 10.1007/s00441-025-03965-3. Online ahead of print.

ABSTRACT

The Na,K-ATPase is a vital transmembrane enzyme, which is important for maintaining cell membrane potentials and the general functionality of animal cells. The enzyme's minimal functional unit consists of one α and one β-subunit, whereas the number of existing paralogs varies in different insect species. The functional roles of different β-subunits, which can account for their diversity within a single species, are so far only partially explained. The emphasis of this study was to specifically elucidate the involvement in septate junctions of the four β-subunits of the new model system Oncopeltus fasciatus. Septate junctions function as a paracellular barrier controlling the flow of solutes across epithelia. So far, studies in Drosophila revealed that nervana2, the β2 homolog of Drosophila, is involved in septate junction formation. In O. fasciatus, we demonstrate that most of the Na,K-ATPase subunits colocalize with septate junction proteins. This agrees with our previous findings implying a role of β2 in the control of tracheal tube size in O. fasciatus, which according to the findings in Drosophila appears to be dependent on a stable formation of septate junctions. Finally, our data suggest a connection between the septate junction protein coracle and the enigmatic, N-terminally strongly truncated βx, which has no obvious homologs in other insects. Our study proposes that the four β-subunits form functional units with septate junction proteins, either allowing tissue-adjusted formation of cell-cell contacts or other yet unknown functions.

PMID:40137937 | DOI:10.1007/s00441-025-03965-3

Pathogens. 2025 Mar 14;14(3):279. doi: 10.3390/pathogens14030279.

ABSTRACT

Helicobacter pylori (H. pylori) possess an arsenal of virulence genes that makes them the main etiological factor in gastric diseases. In this study, 120 southern Moroccan patients who were dyspeptic were profiled to investigate the potential association between disease severity and the combination of multiple virulence genes. Gastric biopsies were taken from patients, followed by histopathological evaluation and genotyping of H. pylori using PCR. H. pylori was detected in 58.3% of cases, and genotypes were distributed as follows: oipA (94.3%), cagA (62.9%), virB11 (60%), babA (55.7%), dupA (54.3%), cagE (51.4%), iceA1 (31.4%), iceA2 (45.7%), vacA s2m2 (47.1%), vacA s1m1 (30%), and vacA s1m2 (7.1%). Statistically significant associations with males were observed for the cagA, cagE, and virB11 genes and multiple strain infections. Multivariate analysis revealed an association between cagE and heightened neutrophil activity, with an odds ratio (OR) of 4.99 (p = 0.03). The gene combination [cagA (+), cagE (+), virB11 (+), vacA s1m1, and babA (+)] emerged as a predictive factor for gastric cancer (OR = 11.10, p = 0.046), while the combination [cagA (-), cagE (-), virB11 (-), vacA s2m2, babA (+)] was associated with gastric atrophy (OR = 10.25, p = 0.016). Age (≤40 years) (OR = 5.87, p = 0.013) and moderate to severe bacterial density (OR = 15.38, p = 0.017) were identified as predictive factors for follicular gastritis. These findings underscore the significance of multigene profiling as a prognostic marker and emphasize the importance of age and sex in preventing adverse outcomes in severe gastric diseases.

PMID:40137764 | DOI:10.3390/pathogens14030279

Pathogens. 2025 Feb 27;14(3):234. doi: 10.3390/pathogens14030234.

ABSTRACT

Mitochondrial genomes serve as essential tools in evolutionary biology, phylogenetics, and population genetics due to their maternal inheritance, lack of recombination, and conserved structure. Traditional morphological methods for identifying nematodes are often insufficient for distinguishing cryptic species complexes. This study highlights recent advancements in nematode mitochondrial genome research, particularly the impact of long-read sequencing technologies such as Oxford Nanopore. These technologies have facilitated the assembly of mitochondrial genomes from mixed soil samples, overcoming challenges associated with designing specific primers for long PCR amplification across different groups of parasitic nematodes. In this study, we successfully recovered and assembled eleven nematode mitochondrial genomes using long-read sequencing, including those of two plant-parasitic nematode species. Notably, we detected Heterodera cruciferae in Victoria, expanding its known geographic range within Australia. Additionally, short-read sequencing data from a previous draft genome study revealed the presence of the mitochondrial genome of Heterodera filipjevi. Comparative analyses of Heterodera mitogenomes revealed conserved protein-coding genes essential for oxidative phosphorylation, as well as gene rearrangements and variations in transfer RNA placement, which may reflect adaptations to parasitic lifestyles. The consistently high A+T content and strand asymmetry observed across species align with trends reported in related genera. This study demonstrates the utility of long-read sequencing for identifying coexisting nematode species in agricultural fields, providing a rapid, accurate, and comprehensive alternative to traditional diagnostic methods. By incorporating non-target endemic species into public databases, this approach enhances biodiversity records and informs biosecurity strategies. These findings reinforce the potential of mitochondrial genomics to strengthen Australia's as well as the global biosecurity framework against plant-parasitic nematode threats.

PMID:40137719 | DOI:10.3390/pathogens14030234

Drug Ther Bull. 2025 Mar 26:dtb-2025-000012. doi: 10.1136/dtb.2025.000012. Online ahead of print.

ABSTRACT

The BNF is jointly published by the Royal Pharmaceutical Society and BMJ. BNF is published in print twice a year and interim updates are issued and published monthly in the digital versions. The following summary provides a brief description of some recent key changes that have been made to BNF content.

PMID:40139730 | DOI:10.1136/dtb.2025.000012

Curr Oncol. 2025 Feb 27;32(3):140. doi: 10.3390/curroncol32030140.

ABSTRACT

The advent of immune checkpoint inhibitors (ICIs) has significantly transformed cancer treatment outcomes. However, these therapies can induce immune-related adverse events (irAEs) that may affect any organ system, sometimes requiring specialized expertise. As ICIs are increasingly used across various tumor types and in earlier treatment settings, not all practitioners have the necessary support network to handle complex irAEs. To address this gap, we collaborated with ONCOassist, a leading app for oncology professionals, to establish the first virtual Canadian Community of Practice (CoP) focused on irAEs. The CoP facilitates continuous learning and improves patient care among Canadian clinicians treating patients with immunotherapy by providing a platform for knowledge exchange and peer-to-peer support. This article outlines the development and growth of the CoP on irAEs, highlighting both successes and challenges. As of May 2024, over a year since its inception, the CoP on irAEs has attracted almost 130 Canadian oncology healthcare professionals, and peer-to-peer interactions and engagement continue to increase. To ensure its long-term sustainability, we plan to evolve and adapt the CoP to meet the needs of the oncology community and address clinical challenges associated with new therapies.

PMID:40136344 | DOI:10.3390/curroncol32030140

J Bioinform Comput Biol. 2025 Mar 25:2550001. doi: 10.1142/S0219720025500015. Online ahead of print.

ABSTRACT

Drug repurposing is the process of identifying new clinical indications for an existing drug. Some of the recent studies utilized drug response prediction models to identify drugs that can be repurposed. By representing cell-line features as a pathway-pathway interaction network, we can better understand the connections between cellular processes and drug response mechanisms. Existing deep learning models for drug response prediction do not integrate known biological pathway-pathway interactions into the model. This paper presents a drug response prediction model that applies a graph convolution operation on a pathway-pathway interaction network to represent features of cancer cell-lines effectively. The model is used to identify potential drug repurposing candidates for Non-Small Cell Lung Cancer (NSCLC). Experiment results show that the inclusion of graph convolutional model applied on a pathway-pathway interaction network makes the proposed model more effective in predicting drug response than the state-of-the-art methods. Specifically, the model has shown better performance in terms of Root Mean Squared Error, Coefficient of Determination, and Pearson's Correlation Coefficient when applied to the GDSC1000 dataset. Also, most of the drugs that the model predicted as top candidates for NSCLC treatment are either undergoing clinical studies or have some evidence in the PubMed literature database.

PMID:40134346 | DOI:10.1142/S0219720025500015

Discov Oncol. 2025 Mar 26;16(1):396. doi: 10.1007/s12672-025-02067-4.

ABSTRACT

The nervous system plays a critical role in developmental biology and oncology, influencing processes from ontogeny to the complex dynamics of cancer progression. Interactions between the nervous system and cancer significantly affect oncogenesis, tumor growth, invasion, metastasis, treatment resistance, inflammation that promotes tumors, and the immune response. A comprehensive understanding of the signal transduction pathways involved in cancer biology is essential for devising effective anti-cancer strategies and overcoming resistance to existing therapies. Recent advances in cancer neuroscience promise to establish a new cornerstone of cancer therapy. Repurposing drugs originally developed for modulating nerve signal transduction represent a promising approach to target oncogenic signaling pathways in cancer treatment. This review endeavors to investigate the potential of repurposing neurological drugs, which target neurotransmitters and neural pathways, for oncological applications. In this context, it aims to bridge the interdisciplinary gap between neurology, psychiatry, internal medicine, and oncology. By leveraging already approved drugs, researchers can utilize existing extensive safety and efficacy data, thereby reducing both the time and financial resources necessary for the development of new cancer therapies. This strategy not only promises to enhance patient outcomes but also to expand the array of available treatments, thereby enriching the therapeutic landscape in oncology.

PMID:40133751 | DOI:10.1007/s12672-025-02067-4