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MLG2Net: Molecular Global Graph Network for Drug Response Prediction in Lung Cancer Cell Lines

J Med Syst. 2025 Apr 10;49(1):47. doi: 10.1007/s10916-025-02182-3.

ABSTRACT

Drug response prediction (DRP) is a central task in the era of precision medicine. Over the past decade, the emergence of deep learning (DL) has greatly contributed to addressing DRP challenges. Notably, the prediction of DRP for cancer cell lines benefits significantly from data availability for model development. However, an effective predictive model is still challenging due to issues with data quality, high-dimensional data, and multi-omics data integration. In this study, we introduce MLG2Net, a deep-learning model inspired by graph neural networks designed to predict DRP in lung cancer cell lines based on pharmacogenomics data. Our model comprises two key components: drug SMILES described by local and global graph networks and cell line genomics are illustrated as a map. Our results show that MLG2Net outperforms three reference graph networks. MLG2Net performance reached a Pearson coefficient correlation ( C C p ) of 0.8616 and a root mean square error (RMSE) of 2.94e-6 in predicting drug responses for Lung Adenocarcinoma (LUAD) cell lines. Subsequent testing on the Lung Squamous Cell Carcinoma (LUSC) dataset reveals lower performance ( C C p : 0.7999, RMSE: 4.08e-6), attributed to the dataset's smaller size influencing model capacity. Moreover, we assessed the model's architecture by isolating its components, with results indicating that the global network is particularly effective in this task. In conclusion, MLG2Net exhibited promising applications in DRP for cancer cell lines, with potential advancements by incorporating larger datasets.

PMID:40208442 | DOI:10.1007/s10916-025-02182-3

MLG2Net: Molecular Global Graph Network for Drug Response Prediction in Lung Cancer Cell Lines

J Med Syst. 2025 Apr 10;49(1):47. doi: 10.1007/s10916-025-02182-3.

ABSTRACT

Drug response prediction (DRP) is a central task in the era of precision medicine. Over the past decade, the emergence of deep learning (DL) has greatly contributed to addressing DRP challenges. Notably, the prediction of DRP for cancer cell lines benefits significantly from data availability for model development. However, an effective predictive model is still challenging due to issues with data quality, high-dimensional data, and multi-omics data integration. In this study, we introduce MLG2Net, a deep-learning model inspired by graph neural networks designed to predict DRP in lung cancer cell lines based on pharmacogenomics data. Our model comprises two key components: drug SMILES described by local and global graph networks and cell line genomics are illustrated as a map. Our results show that MLG2Net outperforms three reference graph networks. MLG2Net performance reached a Pearson coefficient correlation ( C C p ) of 0.8616 and a root mean square error (RMSE) of 2.94e-6 in predicting drug responses for Lung Adenocarcinoma (LUAD) cell lines. Subsequent testing on the Lung Squamous Cell Carcinoma (LUSC) dataset reveals lower performance ( C C p : 0.7999, RMSE: 4.08e-6), attributed to the dataset's smaller size influencing model capacity. Moreover, we assessed the model's architecture by isolating its components, with results indicating that the global network is particularly effective in this task. In conclusion, MLG2Net exhibited promising applications in DRP for cancer cell lines, with potential advancements by incorporating larger datasets.

PMID:40208442 | DOI:10.1007/s10916-025-02182-3

Early Screening and Subtype Identification of High-Risk Lung Nodules via Breathprint by Graphene eNose Platform: A Large Cohort Study

ACS Sens. 2025 Apr 25;10(4):3101-3111. doi: 10.1021/acssensors.5c00314. Epub 2025 Apr 7.

ABSTRACT

Early screening of individuals with high-risk lung nodules can significantly improve the prognosis of lung cancer patients, and accurate identification of lung nodule subtypes can provide guidance for medical treatment. Exhaled breath (EB) analysis via eNoses offers a quick and noninvasive approach, but current eNose technology lacks quality control and solid validation in large population studies. Herein, an eNose platform integrated with a metal ion-decorated graphene sensor array and a breath sampling accessory was established. EB samples from 427 healthy subjects and 2586 subjects with lung nodules, including various benign and malignant subtypes, were collected through the breath sampling accessory for quality control. The large-cohort clinical EB samples were analyzed by the eNose platform to acquire the cross-reactive resistance response. Breathprint analysis for high-risk lung nodules using SVM and age-matched training sets yielded strong and robust performance. Combined with baseline data, the model achieved an AUC of 0.93 (95% CI, 0.89-0.96) on the external test set, with 97% sensitivity and 73% specificity. Moreover, dimensionality reduction analysis of breathprints demonstrated separability across different lung nodule subtypes. This study demonstrates the reliability of the graphene eNose platform to identify high-risk lung nodules and classify lung nodule subtypes in a noninvasive and rapid method.

PMID:40193324 | DOI:10.1021/acssensors.5c00314

Cross-sectional and longitudinal association of seven DNAm-based predictors with metabolic syndrome and type 2 diabetes

To date, various epigenetic clocks have been constructed to estimate biological age, most commonly using DNA methylation (DNAm). These include “first-generation” clocks such as DNAmAgeHorvath and “second-gener...

Spatial multi-omics reveals cell-type-specific nuclear compartments

Nature, Published online: 09 April 2025; doi:10.1038/s41586-025-08838-x

A genomic barcoding scheme called two-layer DNA seqFISH+ enables the simultaneous mapping of more than 100,000 loci and has been used to identify cell-type-specific subnuclear compartments in the mouse brain.
  • ✇MRD
  • Liquid Biopsy in Solid Tumours: An Overview Pasquale Pisapia · Antonino Iaccarino · Giancarlo Troncone · Umberto Malapelle
    Cytopathology. 2025 Apr 11. doi: 10.1111/cyt.13485. Online ahead of print.ABSTRACTThe advent of personalised and precision medicine has radically modified the management and the clinical outcome of cancer patients. However, the expanding number of predictive, prognostic, and diagnostic biomarkers has raised the need for simple, noninvasive, quicker, but equally efficient tests for molecular profiling. In this complex scenario, the adoption of liquid biopsy, particularly circulating tumour DNA (c
     

Liquid Biopsy in Solid Tumours: An Overview

Cytopathology. 2025 Apr 11. doi: 10.1111/cyt.13485. Online ahead of print.

ABSTRACT

The advent of personalised and precision medicine has radically modified the management and the clinical outcome of cancer patients. However, the expanding number of predictive, prognostic, and diagnostic biomarkers has raised the need for simple, noninvasive, quicker, but equally efficient tests for molecular profiling. In this complex scenario, the adoption of liquid biopsy, particularly circulating tumour DNA (ctDNA), has been a real godsend for many cancer patients who would otherwise have been denied the benefits of targeted treatments. Undeniably, ctDNA analysis has several advantages over conventional tissue-based analysis. One advantage is that it can guide treatment decision making, especially when tissue samples are scarce or totally unavailable. Indeed, a simple blood test can inform clinicians on patients' response or resistance to targeted therapies, help them monitor minimal residual disease (MRD) after surgical resections, and facilitate them with early cancer detection and interception. Finally, an equally important advantage is that ctDNA analysis can help decipher temporal and spatial tumour heterogeneity, a mechanism highly responsible for therapeutic resistance. In this review, we gathered and analysed current evidence on the clinical usefulness of ctDNA analysis in solid tumours.

PMID:40219616 | DOI:10.1111/cyt.13485

  • ✇MRD
  • Integration of Liquid Biopsy for Optimal Management of NSCLC Yuko Oya · Ichidai Tanaka · Ross A Soo
    Tuberc Respir Dis (Seoul). 2025 Apr 8. doi: 10.4046/trd.2024.0146. Online ahead of print.ABSTRACTMolecular profiling of tumours from patients plays a crucial role in precision oncology. While tumour tissue-based genomic testing remains the gold standard in clinical management of patients with non-small cell lung cancer, advances in genomic technologies, the analysis of various bodily fluids, mainly blood but also saliva, pleural/ pericardial effusions, urine, and cerebrospinal fluid is now feasi
     

Integration of Liquid Biopsy for Optimal Management of NSCLC

8 April 2025 at 18:00

Tuberc Respir Dis (Seoul). 2025 Apr 8. doi: 10.4046/trd.2024.0146. Online ahead of print.

ABSTRACT

Molecular profiling of tumours from patients plays a crucial role in precision oncology. While tumour tissue-based genomic testing remains the gold standard in clinical management of patients with non-small cell lung cancer, advances in genomic technologies, the analysis of various bodily fluids, mainly blood but also saliva, pleural/ pericardial effusions, urine, and cerebrospinal fluid is now feasible and readily available. In this review, we will focus on the clinical application of circulating tumour DNA in patients with non-small cell lung cancer in the setting of early-stage disease, locally advanced disease with attention to the potential of ctDNA in prognostication, risk stratification, minimal residual disease, and in advanced disease, its role in the detection of genomic markers and mechanisms of acquired resistance. The role of ctDNA and liquid biopsies in lung cancer screening will also be discussed.

PMID:40195729 | DOI:10.4046/trd.2024.0146

A multiomics dataset of paired CT image and plasma cell-free DNA end motif for patients with pulmonary nodules

Sci Data. 2025 Apr 1;12(1):545. doi: 10.1038/s41597-025-04912-1.

ABSTRACT

Diagnosing lung cancer at a curable stage offers the opportunity for a favorable prognosis. The emerging epigenomics analysis on plasma cell-free DNA (cfDNA), including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) modifications, has acted as a promising approach facilitating the identification of lung cancer. And, integrating 5mC biomarker with chest computed tomography (CT) image features could optimize the diagnosis of lung cancer, exceeding the performance of models built on single feature. However, the clinical applicability of integrated markers might be limited by the potential risk of overfitting due to small sample size. Hence, we prospectively collected peripheral blood sample and the paired chest CT images of 2032 patients with indeterminate pulmonary nodules across 5 centers, and constructed a large-scale, multi-institutional, multiomics database that encompass CT imaging data and plasma cfDNA fragmentomic in 5mC-, 5hmC-enriched regions. To our best knowledge, this dataset is the first radio-epigenomic dataset with the largest sample size, and provides multi-dimensional insights for early diagnosis of lung cancer, facilitating the individuated management for lung cancer.

PMID:40169596 | PMC:PMC11961589 | DOI:10.1038/s41597-025-04912-1

Translating the multifaceted use of liquid biopsy to management of early disease in pancreatic adenocarcinoma

Front Oncol. 2025 Mar 13;15:1520717. doi: 10.3389/fonc.2025.1520717. eCollection 2025.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality, primarily due to late stage at diagnosis. This review examines the multifaceted applications of liquid biopsy and circulating tumor DNA (ctDNA) analysis in the diagnosis and management of PDAC. We review the current literature on the technological advancements in liquid biopsy analysis such as next generation sequencing (NGS) and digital droplet PCR (ddPCR) as well as multi-omics technologies, highlighting their potential for accurate molecular subtyping through ctDNA analysis. This review highlights the significant role of ctDNA in the assessment of tumor behavior, disease subtyping, prediction and monitoring of treatment response, and evaluation of minimal residual disease. We discuss the implications of integrating liquid biopsy techniques into clinical practice as well as its challenges and limitations. By drawing insights from recent studies, this review aims to provide a comprehensive overview of how liquid biopsy and ctDNA analysis can enhance early disease management strategies in PDAC. We underscore the need for additional prospective studies and clinical trials to validate its feasibility and accuracy in order to establish clinical utility, with the ultimate goal of routine incorporation into practice to improve patient outcomes and transform the treatment landscape for PDAC.

PMID:40182037 | PMC:PMC11966063 | DOI:10.3389/fonc.2025.1520717

Integrated multi-omics landscape of non-small cell lung cancer with distant metastasis

Front Immunol. 2025 Mar 17;16:1560724. doi: 10.3389/fimmu.2025.1560724. eCollection 2025.

ABSTRACT

BACKGROUND: Distant metastasis is one of the important factors affecting the prognosis of lung cancer patients. Extracellular vesicles (EVs) play an important role in the occurrence, development, and metastasis of cancer. However, it is currently unclear whether EVs in BALF are involved in distant tumor metastasis.

METHODS: we collected bronchoalveolar lavage fluid (BALF) from patients with metastatic and non-metastatic non-small cell lung cancer (NSCLC) to isolate exosomes, which were then characterized by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), followed by comprehensive metabolomic and proteomic analysis to ultimately construct a distant metastasis prediction model for non-small cell lung cancer.

RESULTS: Our research has found that the BALF of NSCLC patients is rich in EVs, which have typical morphology and size. There are significant differences in protein expression and metabolite types between patients with distant metastasis and those without distant metastasis. Sphingolipid metabolism pathways may be a key factor influencing distant metastasis in NSCLC. Subsequently, we constructed a predictive model for distant metastasis in NSCLC based on differentially expressed proteins identified by proteomics. This model has been proven to have high predictive value.

CONCLUSION: The multi-omic analysis generated in this study provided a global overview of the molecular changes, which may provide useful insight into the therapy and prognosis of NSCLC metastasis.

PMID:40165954 | PMC:PMC11956740 | DOI:10.3389/fimmu.2025.1560724

Translating the multifaceted use of liquid biopsy to management of early disease in pancreatic adenocarcinoma

4 April 2025 at 18:00

Front Oncol. 2025 Mar 13;15:1520717. doi: 10.3389/fonc.2025.1520717. eCollection 2025.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality, primarily due to late stage at diagnosis. This review examines the multifaceted applications of liquid biopsy and circulating tumor DNA (ctDNA) analysis in the diagnosis and management of PDAC. We review the current literature on the technological advancements in liquid biopsy analysis such as next generation sequencing (NGS) and digital droplet PCR (ddPCR) as well as multi-omics technologies, highlighting their potential for accurate molecular subtyping through ctDNA analysis. This review highlights the significant role of ctDNA in the assessment of tumor behavior, disease subtyping, prediction and monitoring of treatment response, and evaluation of minimal residual disease. We discuss the implications of integrating liquid biopsy techniques into clinical practice as well as its challenges and limitations. By drawing insights from recent studies, this review aims to provide a comprehensive overview of how liquid biopsy and ctDNA analysis can enhance early disease management strategies in PDAC. We underscore the need for additional prospective studies and clinical trials to validate its feasibility and accuracy in order to establish clinical utility, with the ultimate goal of routine incorporation into practice to improve patient outcomes and transform the treatment landscape for PDAC.

PMID:40182037 | PMC:PMC11966063 | DOI:10.3389/fonc.2025.1520717

20 years of histone lysine demethylases: From discovery to the clinic and beyond

Histone lysine demethylases are conserved enzymes that remove methyl groups from histone proteins and play important roles in development and disease. On the 20th anniversary of their discovery, this Review provides an in-depth view of their functions and roles across various contexts as well as therapeutic options to be developed for diseases related to these enzymes.

Synonymous mutations promote tumorigenesis by disrupting m6A-dependent mRNA metabolism

13 February 2025 at 08:00
The impact of synonymous mutations remains elusive. Here, the authors demonstrate that synonymous mutations can promote tumorigenesis by disrupting post-transcriptional m6A modification. The findings provide fresh insights into understanding the genotype-phenotype relationship in cancer and beyond.

Treatment of advanced-stage non-small cell lung cancer: Current progress and a glimpse into the future (Review)

Mol Clin Oncol. 2025 Mar 12;22(5):42. doi: 10.3892/mco.2025.2837. eCollection 2025 May.

ABSTRACT

Before the twentieth century, patients with advanced lung cancer had limited treatment options and chemotherapy was the primary form of treatment, with an overall survival often <0.5 years. However, with advances in society and medical technology, the treatment approaches for advanced non-small cell lung cancer (NSCLC) have markedly changed. Traditional chemotherapy has been gradually replaced by targeted therapy and immunotherapy, leading to the emergence of various new therapeutic options that offer patients more personalized and precise care. This raises the question of what the future holds for the treatment of NSCLC. This review provides a comprehensive analysis of the latest breakthroughs in targeted therapies, immunotherapies, and drugs for antibody-drug conjugates (ADCs), highlights advances in multimodal combination therapy strategies, and explores the causes of resistance and the challenges that exist in overcoming it. In particular, this review provides unique insights into key directions for future research in NSCLC, such as personalised treatment strategies and biomarker exploration based on multi-omics data, aiming to provide new inspiration for clinical decision-making and research.

PMID:40160297 | PMC:PMC11948471 | DOI:10.3892/mco.2025.2837

  • ✇MIT Technology Review
  • Cyberattacks by AI agents are coming Rhiannon Williams
    Agents are the talk of the AI industry—they’re capable of planning, reasoning, and executing complex tasks like scheduling meetings, ordering groceries, or even taking over your computer to change settings on your behalf. But the same sophisticated abilities that make agents helpful assistants could also make them powerful tools for conducting cyberattacks. They could readily be used to identify vulnerable targets, hijack their systems, and steal valuable data from unsuspecting victims.   At
     

Cyberattacks by AI agents are coming

4 April 2025 at 18:32

Agents are the talk of the AI industry—they’re capable of planning, reasoning, and executing complex tasks like scheduling meetings, ordering groceries, or even taking over your computer to change settings on your behalf. But the same sophisticated abilities that make agents helpful assistants could also make them powerful tools for conducting cyberattacks. They could readily be used to identify vulnerable targets, hijack their systems, and steal valuable data from unsuspecting victims.  

At present, cybercriminals are not deploying AI agents to hack at scale. But researchers have demonstrated that agents are capable of executing complex attacks (Anthropic, for example, observed its Claude LLM successfully replicating an attack designed to steal sensitive information), and cybersecurity experts warn that we should expect to start seeing these types of attacks spilling over into the real world.

“I think ultimately we’re going to live in a world where the majority of cyberattacks are carried out by agents,” says Mark Stockley, a security expert at the cybersecurity company Malwarebytes. “It’s really only a question of how quickly we get there.”

While we have a good sense of the kinds of threats AI agents could present to cybersecurity, what’s less clear is how to detect them in the real world. The AI research organization Palisade Research has built a system called LLM Agent Honeypot in the hopes of doing exactly this. It has set up vulnerable servers that masquerade as sites for valuable government and military information to attract and try to catch AI agents attempting to hack in.

The team behind it hopes that by tracking these attempts in the real world, the project will act as an early warning system and help experts develop effective defenses against AI threat actors by the time they become a serious issue.

“Our intention was to try and ground the theoretical concerns people have,” says Dmitrii Volkov, research lead at Palisade. “We’re looking out for a sharp uptick, and when that happens, we’ll know that the security landscape has changed. In the next few years, I expect to see autonomous hacking agents being told: ‘This is your target. Go and hack it.’”

AI agents represent an attractive prospect to cybercriminals. They’re much cheaper than hiring the services of professional hackers and could orchestrate attacks more quickly and at a far larger scale than humans could. While cybersecurity experts believe that ransomware attacks—the most lucrative kind—are relatively rare because they require considerable human expertise, those attacks could be outsourced to agents in the future, says Stockley. “If you can delegate the work of target selection to an agent, then suddenly you can scale ransomware in a way that just isn’t possible at the moment,” he says. “If I can reproduce it once, then it’s just a matter of money for me to reproduce it 100 times.”

Agents are also significantly smarter than the kinds of bots that are typically used to hack into systems. Bots are simple automated programs that run through scripts, so they struggle to adapt to unexpected scenarios. Agents, on the other hand, are able not only to adapt the way they engage with a hacking target but also to avoid detection—both of which are beyond the capabilities of limited, scripted programs, says Volkov. “They can look at a target and guess the best ways to penetrate it,” he says. “That kind of thing is out of reach of, like, dumb scripted bots.”

Since LLM Agent Honeypot went live in October of last year, it has logged more than 11 million attempts to access it—the vast majority of which were from curious humans and bots. But among these, the researchers have detected eight potential AI agents, two of which they have confirmed are agents that appear to originate from Hong Kong and Singapore, respectively. 

“We would guess that these confirmed agents were experiments directly launched by humans with the agenda of something like ‘Go out into the internet and try and hack something interesting for me,’” says Volkov. The team plans to expand its honeypot into social media platforms, websites, and databases to attract and capture a broader range of attackers, including spam bots and phishing agents, to analyze future threats.  

To determine which visitors to the vulnerable servers were LLM-powered agents, the researchers embedded prompt-injection techniques into the honeypot. These attacks are designed to change the behavior of AI agents by issuing them new instructions and asking questions that require humanlike intelligence. This approach wouldn’t work on standard bots.

For example, one of the injected prompts asked the visitor to return the command “cat8193” to gain access. If the visitor correctly complied with the instruction, the researchers checked how long it took to do so, assuming that LLMs are able to respond in much less time than it takes a human to read the request and type out an answer—typically in under 1.5 seconds. While the two confirmed AI agents passed both tests, the six others only entered the command but didn’t meet the response time that would identify them as AI agents.

Experts are still unsure when agent-orchestrated attacks will become more widespread. Stockley, whose company Malwarebytes named agentic AI as a notable new cybersecurity threat in its 2025 State of Malware report, thinks we could be living in a world of agentic attackers as soon as this year. 

And although regular agentic AI is still at a very early stage—and criminal or malicious use of agentic AI even more so—it’s even more of a Wild West than the LLM field was two years ago, says Vincenzo Ciancaglini, a senior threat researcher at the security company Trend Micro. 

“Palisade Research’s approach is brilliant: basically hacking the AI agents that try to hack you first,” he says. “While in this case we’re witnessing AI agents trying to do reconnaissance, we’re not sure when agents will be able to carry out a full attack chain autonomously. That’s what we’re trying to keep an eye on.” 

And while it’s possible that malicious agents will be used for intelligence gathering before graduating to simple attacks and eventually complex attacks as the agentic systems themselves become more complex and reliable, it’s equally possible there will be an unexpected overnight explosion in criminal usage, he says: “That’s the weird thing about AI development right now.”

Those trying to defend against agentic cyberattacks should keep in mind that AI is currently more of an accelerant to existing attack techniques than something that fundamentally changes the nature of attacks, says Chris Betz, chief information security officer at Amazon Web Services. “Certain attacks may be simpler to conduct and therefore more numerous; however, the foundation of how to detect and respond to these events remains the same,” he says.

Agents could also be deployed to detect vulnerabilities and protect against intruders, says Edoardo Debenedetti, a PhD student at ETH Zürich in Switzerland, pointing out that if a friendly agent cannot find any vulnerabilities in a system, it’s unlikely that a similarly capable agent used by a malicious party is going to be able to find any either.

While we know that AI’s potential to autonomously conduct cyberattacks is a growing risk and that AI agents are already scanning the internet, one useful next step is to evaluate how good agents are at finding and exploiting these real-world vulnerabilities. Daniel Kang, an assistant professor at the University of Illinois Urbana-Champaign, and his team have built a benchmark to evaluate this; they have found that current AI agents successfully exploited up to 13% of vulnerabilities for which they had no prior knowledge. Providing the agents with a brief description of the vulnerability pushed the success rate up to 25%, demonstrating how AI systems are able to identify and exploit weaknesses even without training. Basic bots would presumably do much worse.

The benchmark provides a standardized way to assess these risks, and Kang hopes it can guide the development of safer AI systems. “I’m hoping that people start to be more proactive about the potential risks of AI and cybersecurity before it has a ChatGPT moment,” he says. “I’m afraid people won’t realize this until it punches them in the face.”

Molecular mechanisms and therapeutic targets of acute exacerbations of chronic obstructive pulmonary disease with Pseudomonas aeruginosa infection

Respir Res. 2025 Mar 26;26(1):115. doi: 10.1186/s12931-025-03185-x.

ABSTRACT

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of global mortality, with acute exacerbations of COPD (AECOPD) significantly increasing the disease's morbidity and mortality. Among the pathogens implicated in AECOPD, Pseudomonas aeruginosa (P. aeruginosa) is increasingly recognized as a major co-infecting bacterium. Despite its clinical importance, the molecular mechanisms and therapeutic targets underlying AECOPD with P. aeruginosa infection remain inadequately understood.

METHODS: We employed a multi-omics approach, integrating proteomic analyses of bronchoalveolar lavage fluid (BALF) and plasma with transcriptomic analysis of peripheral blood. A discovery cohort of 40 AECOPD with P. aeruginosa infection patients and 20 healthy controls was analyzed, followed by validation in an independent cohort of 20 patients and 10 controls. Differentially expressed proteins (DEPs) and genes (DEGs) were identified and subjected to protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis (WGCNA), and immune infiltration analysis. Molecular docking simulations were conducted to explore potential therapeutic agents.

RESULTS: Our integrative analysis identified key biomarkers, which played critical roles in oxidative stress and neutrophil extracellular trap (NET) formation, both of which were pivotal in the pathogenesis of AECOPD with P. aeruginosa infection. The combined analysis of BALF, plasma, and peripheral blood underscored the interplay between local lung changes and systemic immune responses. Functional enrichment analyses highlighted significant pathways related to bacterial defense, inflammation, and immune activation. Validation in an independent cohort confirmed the diagnostic value of three key proteins (AZU1, MPO, and RETN), with high area under the curve (AUC) values in ROC analyses. Molecular docking indicated strong binding affinities of these proteins with Pioglitazone and Rosiglitazone, suggesting potential therapeutic utility.

CONCLUSIONS: This study provides a comprehensive understanding of the molecular mechanisms underlying AECOPD with P. aeruginosa infection, highlighting the pivotal roles of oxidative stress and NET formation in disease progression. The identified biomarkers offer promising diagnostic and therapeutic targets. Our findings pave the way for novel strategies to improve outcomes for AECOPD patients with P. aeruginosa infection. While the study design limits our ability to establish causality, these results provide important insights that warrant further investigation, particularly through longitudinal studies, to confirm the specific contributions of P. aeruginosa in exacerbations.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40140846 | PMC:PMC11948814 | DOI:10.1186/s12931-025-03185-x

Liquid Biopsies in the Early Diagnosis, Prognosis, and Tailored Treatment of Colorectal Cancer

Cancers (Basel). 2025 Mar 8;17(6):927. doi: 10.3390/cancers17060927.

ABSTRACT

INTRODUCTION: Liquid biopsies provide a less-invasive option to tissue biopsies for the early diagnosis, prognosis, and tailored therapy of colorectal cancer (CRC). CRC is a major cause of cancer-related death, and early identification is essential for improving patient outcomes.

REVIEW: Conventional diagnostic techniques, including colonoscopy and tissue biopsy, may be enhanced by liquid biopsies that examine circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and other indicators present in body fluids. These markers provide significant insights into tumor biology, heterogeneity, and therapeutic response. CTCs detected in early-stage CRC have prognostic significance for disease recurrence and survival, while ctDNA investigation may uncover genetic mutations, epigenetic alterations, and tumor development. The identification of ctDNA in minimal residual disease (MRD) postsurgery correlates with an elevated risk of recurrence and unfavorable prognosis, underscoring its use in assessing treatment effectiveness. Furthermore, non-coding RNAs (ncRNAs) contained inside EVs provide potential prospective biomarkers and therapeutic targets, facilitating diagnosis and treatment assessment. Notwithstanding the potential of liquid biopsies, obstacles persist in assay standardization, sensitivity enhancement, and the management of tumor heterogeneity. Additional extensive research is required to determine their function in clinical practice.

CONCLUSION: Overall, liquid biopsies serve as a potential instrument for real-time monitoring, evaluating therapy responses, and directing individualized therapeutic strategies in CRC patients.

PMID:40149264 | PMC:PMC11940745 | DOI:10.3390/cancers17060927

  • ✇MRD
  • Liquid biopsies in cancer Hang Yin · Manjie Zhang · Yu Zhang · Xuebing Zhang · Xia Zhang · Bin Zhang
    Mol Biomed. 2025 Mar 20;6(1):18. doi: 10.1186/s43556-025-00257-8.ABSTRACTCancer ranks among the most lethal diseases worldwide. Tissue biopsy is currently the primary method for the diagnosis and biological analysis of various solid tumors. However, this method has some disadvantages related to insufficient tissue specimen collection and intratumoral heterogeneity. Liquid biopsy is a noninvasive approach for identifying cancer-related biomarkers in peripheral blood, which allows for repetitive s
     

Liquid biopsies in cancer

20 March 2025 at 18:00

Mol Biomed. 2025 Mar 20;6(1):18. doi: 10.1186/s43556-025-00257-8.

ABSTRACT

Cancer ranks among the most lethal diseases worldwide. Tissue biopsy is currently the primary method for the diagnosis and biological analysis of various solid tumors. However, this method has some disadvantages related to insufficient tissue specimen collection and intratumoral heterogeneity. Liquid biopsy is a noninvasive approach for identifying cancer-related biomarkers in peripheral blood, which allows for repetitive sampling across multiple time points. In the field of liquid biopsy, representative biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. Many studies have evaluated the prognostic and predictive roles of CTCs and ctDNA in various solid tumors. Although these studies have limitations, the results of most studies appear to consistently demonstrate the correlations of high CTC counts and ctDNA mutations with lower survival rates in cancer patients. Similarly, a reduction in CTC counts throughout therapy may be a potential prognostic indicator related to treatment response in advanced cancer patients. Moreover, the biochemical characteristics of CTCs and ctDNA can provide information about tumor biology as well as resistance mechanisms against targeted therapy. This review discusses the current clinical applications of liquid biopsy in cancer patients, emphasizing its possible utility in outcome prediction and treatment decision-making.

PMID:40108089 | PMC:PMC11923355 | DOI:10.1186/s43556-025-00257-8

  • ✇MIT Technology Review
  • How a bankruptcy judge can stop a genetic privacy disaster Keith Porcaro
    Stop me if you’ve heard this one before: A tech company accumulates a ton of user data, hoping to figure out a business model later. That business model never arrives, the company goes under, and the data is in the wind.  The latest version of that story emerged on March 24, when the onetime genetic testing darling 23andMe filed for bankruptcy. Now the fate of 15 million people’s genetic data rests in the hands of a bankruptcy judge. At a hearing on March 26, the judge gave 23andMe permission
     

How a bankruptcy judge can stop a genetic privacy disaster

28 March 2025 at 21:00

Stop me if you’ve heard this one before: A tech company accumulates a ton of user data, hoping to figure out a business model later. That business model never arrives, the company goes under, and the data is in the wind. 

The latest version of that story emerged on March 24, when the onetime genetic testing darling 23andMe filed for bankruptcy. Now the fate of 15 million people’s genetic data rests in the hands of a bankruptcy judge. At a hearing on March 26, the judge gave 23andMe permission to seek offers for its users’ data. But, there’s still a small chance of writing a better ending for users.

After the bankruptcy filing, the immediate take from policymakers and privacy advocates was that 23andMe users should delete their accounts to prevent genetic data from falling into the wrong hands. That’s good advice for the individual user (and you can read how to do so here). But the reality is most people won’t do it. Maybe they won’t see the recommendations to do so. Maybe they don’t know why they should be worried. Maybe they have long since abandoned an account that they don’t even remember exists. Or maybe they’re just occupied with the chaos of everyday life. 

This means the real value of this data comes from the fact that people have forgotten about it. Given 23andMe’s meager revenue—fewer than 4% of people who took tests pay for subscriptions—it seems inevitable that the new owner, whoever it is, will have to find some new way to monetize that data. 

This is a terrible deal for users who just wanted to learn a little more about themselves or their ancestry. Because genetic data is forever. Contact information can go stale over time: you can always change your password, your email, your phone number, or even your address. But a bad actor who has your genetic data—whether a cybercriminal selling it to the highest bidder, a company building a profile of your future health risk, or a government trying to identify you—will have it tomorrow and the next day and all the days after that. 

Users with exposed genetic data are not only vulnerable to harm today; they’re vulnerable to exploits that might be developed in the future. 

While 23andMe promises that it will not voluntarily share data with insurance providers, employers, or public databases, its new owner could unwind those promises at any time with a simple change in terms. 

In other words: If a bankruptcy court makes a mistake authorizing the sale of 23andMe’s user data, that mistake is likely permanent and irreparable. 

All this is possible because American lawmakers have neglected to meaningfully engage with digital privacy for nearly a quarter-century. As a result, services are incentivized to make flimsy, deceptive promises that can be abandoned at a moment’s notice. And the burden falls on users to keep track of it all, or just give up.

Here, a simple fix would be to reverse that burden. A bankruptcy court could require that users individually opt in before their genetic data can be transferred to 23andMe’s new owners, regardless of who those new owners are. Anyone who didn’t respond or who opted out would have the data deleted. 

Bankruptcy proceedings involving personal data don’t have to end badly. In 2000, the Federal Trade Commission settled with the bankrupt retailer ToySmart to ensure that its customer data could not be sold as a stand-alone asset, and that customers would have to affirmatively consent to unexpected new uses of their data. And in 2015, the FTC intervened in the bankruptcy of RadioShack to ensure that it would keep its promises never to sell the personal data of its customers. (RadioShack eventually agreed to destroy it.) 

The ToySmart case also gave rise to the role of the consumer privacy ombudsman. Bankruptcy judges can appoint an ombuds to help the court consider how the sale of personal data might affect the bankruptcy estate, examining the potential harms or benefits to consumers and any alternatives that might mitigate those harms. The U.S. Trustee has requested the appointment of an ombuds in this case. While scholars have called for the role to have more teeth and for the FTC and states to intervene more often, a framework for protecting personal data in bankruptcy is available. And ultimately, the bankruptcy judge has broad power to make decisions about how (or whether) property in bankruptcy is sold.

Here, 23andMe has a more permissive privacy policy than ToySmart or RadioShack. But the risks incurred if genetic data falls into the wrong hands or is misused are severe and irreversible. And given 23andMe’s failure to build a viable business model from testing kits, it seems likely that a new business would use genetic data in ways that users wouldn’t expect or want. 

An opt-in requirement for genetic data solves this problem. Genetic data (and other sensitive data) could be held by the bankruptcy trustee and released as individual users gave their consent. If users failed to opt in after a period of time, the remaining data would be deleted. This would incentivize 23andMe’s new owners to earn user trust and build a business that delivers value to users, instead of finding unexpected ways to exploit their data. And it would impose virtually no burden on the people whose genetic data is at risk: after all, they have plenty more DNA to spare.

Consider the alternative. Before 23andMe went into bankruptcy, its then-CEO made two failed attempts to buy it, at reported valuations of $74.7 million and $12.1 million. Using the higher offer, and with 15 million users, that works out to a little under $5 per user. Is it really worth it to permanently risk a person’s genetic privacy just to add a few dollars in value to the bankruptcy estate?    

Of course, this raises a bigger question: Why should anyone be able to buy the genetic data of millions of Americans in a bankruptcy proceeding? The answer is simple: Lawmakers allow them to. Federal and state inaction allows companies to dissolve promises about protecting Americans’ most sensitive data at a moment’s notice. When 23andMe was founded, in 2006, the promise was that personalized health care was around the corner. Today, 18 years later, that era may really be almost here. But with privacy laws like ours, who would trust it?

Keith Porcaro is the Rueben Everett Senior Lecturing Fellow at Duke Law School.

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