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  • ✇MIT Technology Review
  • A Chinese firm has just launched a constantly changing set of AI benchmarks Caiwei Chen
    When testing an AI model, it’s hard to tell if it is reasoning or just regurgitating answers from its training data. Xbench, a new benchmark developed by the Chinese venture capital firm HSG, or HongShan Capital Group, might help to sidestep that issue. That’s thanks to the way it evaluates models not only on the ability to pass arbitrary tests, like most other benchmarks, but also on the ability to execute real-world tasks, which is more unusual. It will be updated on a regular basis to try to
     

A Chinese firm has just launched a constantly changing set of AI benchmarks

23 June 2025 at 23:46

When testing an AI model, it’s hard to tell if it is reasoning or just regurgitating answers from its training data. Xbench, a new benchmark developed by the Chinese venture capital firm HSG, or HongShan Capital Group, might help to sidestep that issue. That’s thanks to the way it evaluates models not only on the ability to pass arbitrary tests, like most other benchmarks, but also on the ability to execute real-world tasks, which is more unusual. It will be updated on a regular basis to try to keep it evergreen. 

This week the company is making part of its question set open-source and letting anyone use for free. The team has also released a leaderboard comparing how mainstream AI models stack up when tested on Xbench. (ChatGPT o3 ranked first across all categories, though ByteDance’s Doubao, Gemini 2.5 Pro, and Grok all still did pretty well, as did Claude Sonnet.) 

Development of the benchmark at HongShan began in 2022, following ChatGPT’s breakout success, as an internal tool for assessing which models are worth investing in. Since then, led by partner Gong Yuan, the team has steadily expanded the system, bringing in outside researchers and professionals to help refine it. As the project grew more sophisticated, they decided to release it to the public.

Xbench approached the problem with two different systems. One is similar to traditional benchmarking: an academic test that gauges a model’s aptitude on various subjects. The other is more like a technical interview round for a job, assessing how much real-world economic value a model might deliver.

Xbench’s methods for assessing raw intelligence currently include two components: Xbench-ScienceQA and Xbench-DeepResearch. ScienceQA isn’t a radical departure from existing postgraduate-level STEM benchmarks like GPQA and SuperGPQA. It includes questions spanning fields from biochemistry to orbital mechanics, drafted by graduate students and double-checked by professors. Scoring rewards not only the right answer but also the reasoning chain that leads to it.

DeepResearch, by contrast, focuses on a model’s ability to navigate the Chinese-language web. Ten subject-matter experts created 100 questions in music, history, finance, and literature—questions that can’t just be googled but require significant research to answer. Scoring favors breadth of sources, factual consistency, and a model’s willingness to admit when there isn’t enough data. A question in the publicized collection is “How many Chinese cities in the three northwestern provinces border a foreign country?” (It’s 12, and only 33% of models tested got it right, if you are wondering.)

On the company’s website, the researchers said they want to add more dimensions to the test—for example, aspects like how creative a model is in its problem solving, how collaborative it is when working with other models, and how reliable it is.

The team has committed to updating the test questions once a quarter and to maintain a half-public, half-private data set.

To assess models’ real-world readiness, the team worked with experts to develop tasks modeled on actual workflows, initially in recruitment and marketing. For example, one task asks a model to source five qualified battery engineer candidates and justify each pick. Another asks it to match advertisers with appropriate short-video creators from a pool of over 800 influencers.

The website also teases upcoming categories, including finance, legal, accounting, and design. The question sets for these categories have not yet been open-sourced.

ChatGPT-o3 again ranks first in both of the current professional categories. For recruiting, Perplexity Search and Claude 3.5 Sonnet take second and third place, respectively. For marketing, Claude, Grok, and Gemini all perform well.

“It is really difficult for benchmarks to include things that are so hard to quantify,” says Zihan Zheng, the lead researcher on a new benchmark called LiveCodeBench Pro and a student at NYU. “But Xbench represents a promising start.”

  • ✇MIT Technology Review
  • Scaling integrated digital health MIT Technology Review Insights
    Around the world, countries are facing the challenges of aging populations, growing rates of chronic disease, and workforce shortages, leading to a growing burden on health care systems. From diagnosis to treatment, AI and other digital solutions can enhance the efficiency and effectiveness of health care, easing the burden on straining systems. According to the World Health Organization (WHO), spending an additional $0.24 per patient per year on digital health interventions could save more than
     

Scaling integrated digital health

Around the world, countries are facing the challenges of aging populations, growing rates of chronic disease, and workforce shortages, leading to a growing burden on health care systems. From diagnosis to treatment, AI and other digital solutions can enhance the efficiency and effectiveness of health care, easing the burden on straining systems. According to the World Health Organization (WHO), spending an additional $0.24 per patient per year on digital health interventions could save more than two million lives from non-communicable diseases over the next decade.

To work most effectively, digital solutions need to be scaled and embedded in an ecosystem that ensures a high degree of interoperability, data security, and governance. If not, the proliferation of point solutions— where specialized software or tools focus on just one specific area or function—could lead to silos and digital canyons, complicating rather than easing the workloads of health care professionals, and potentially impacting patient treatment. Importantly, technologies that enhance workforce productivity should keep humans in the loop, aiming to augment their capabilities, rather than replace them. 

Through a survey of 300 health care executives and a program of interviews with industry experts, startup leaders, and academic researchers, this report explores the best practices for success when implementing integrated digital solutions into health care, and how these can support decision-makers in a range of settings, including laboratories and hospitals. 


Key findings include: 


Health care is primed for digital adoption. The global pandemic underscored the benefits of value-based care and accelerated the adoption of digital and AI-powered technologies in health care. Overwhelmingly, 96% of the survey respondents say they are “ready and resourced” to use digital health, while one in four say they are “very ready.” However, 91% of executives agree interoperability is a challenge, with a majority (59%) saying it will be “tough” to solve. Two in five leaders say balancing security with usability is the biggest challenge for digital health. With the adoption of cloud solutions, organizations can enjoy the benefits of modernized IT infrastructure: 36% of the survey respondents believe scalability is the main benefit, followed by improved security (28%). 

Digital health care can help health care institutions transform patient outcomes—if built on the right foundations. Solutions like AI-powered diagnostics, telemedicine, and remote monitoring can offer measurable impact across the patient journey, from improving early disease detection to reducing hospital readmission rates. However, these technologies can only support fully connected health care when scaled up and embedded in ecosystems with robust data governance, interoperability, and security. 

Health care data has immense potential—but fragmentation and poor interoperability hinder impact. Health care systems generate vast quantities of data, yet much of it remains siloed or unusable due to inconsistent formats and incompatible IT systems, limiting scalability. 

Digital tools must augment, not overload, the workforce. With global health care workforce shortages worsening, digital solutions like clinical decision support tools, patient prediction, and remote monitoring can be seen as essential aids rather than threats to the workforce. Successful deployment depends on usability, clinician engagement, and training. 

Regulatory evolution, open data policies, and economic sustainability are key to scaling digital health. Even the best digital tools struggle to scale without reimbursement frameworks, regulatory support, and viable business models. Open data ecosystems are needed to unleash the clinical and economic value of innovation. Regulatory and reimbursement innovation is also critical to transitioning from pilot projects to high-impact, system-wide adoption.

Download the full report.

This content was produced by Insights, the custom content arm of MIT Technology Review. It was not written by MIT Technology Review’s editorial staff.

This content was researched, designed, and written entirely by human writers, editors, analysts, and illustrators. This includes the writing of surveys and collection of data for surveys. AI tools that may have been used were limited to secondary production processes that passed thorough human review.

Want to know where VCs are investing next? Be in the room at TechCrunch Disrupt 2025

23 June 2025 at 22:30
Early-stage founders, listen up! You will want a front row seat at the Builders Stage on October 27 at 1:00 p.m. PT. This session at TechCrunch Disrupt 2025 brings together Nina Achadjian, partner, Index Ventures; Jerry Chen, general partner, Greylock; and Viviana Faga, general partner, Felicis, all of whom will share their 2026 investment priorities […]

Integrated spatial omics of metabolic reprogramming and the tumor microenvironment in pancreatic cancer

iScience. 2025 May 15;28(6):112681. doi: 10.1016/j.isci.2025.112681. eCollection 2025 Jun 20.

ABSTRACT

Metabolic reprogramming is a defining feature of pancreatic cancer, influencing tumor progression and the tumor microenvironment. By integrating single-cell transcriptomics, spatial transcriptomics, and spatial metabolomics, this study visualized the spatial co-localization of metabolites and gene expression within tumor samples, uncovering metabolic heterogeneity and intercellular interactions. Spatial transcriptomics identified distinct pathological regions, which were further characterized using single-cell transcriptomic data and pathologist annotations. Pseudotime trajectory analysis revealed metabolic shifts along the malignant progression, while single-cell Metabolism (scMetabolism) delineated metabolic differences between pathological regions, classifying them as hypermetabolic or hypometabolic. Notably, aberrant cell communication between cancer cells, macrophages, and fibroblasts was observed, with key receptor-ligand pairs significantly co-expressed in malignant regions and correlated with poor prognosis. Spatial metabolomics imaging identified signature metabolites, highlighting metabolic alterations in amino acid metabolism, polyamine metabolism, fatty acid synthesis, and phospholipid metabolism. This integrated analysis provides critical insights into pancreatic cancer metabolism, offering potential avenues for targeted therapeutic interventions.

PMID:40538442 | PMC:PMC12177182 | DOI:10.1016/j.isci.2025.112681

Advancements in liquid biopsy for breast Cancer: Molecular biomarkers and clinical applications

Cancer Treat Rev. 2025 Jun 14;139:102979. doi: 10.1016/j.ctrv.2025.102979. Online ahead of print.

ABSTRACT

Breast cancer is characterized by significant molecular heterogeneity; therefore, there are distinct clinical features, treatment modalities, and prognostic outcomes across its various molecular subtypes. In the era of precision medicine, liquid biopsy has emerged as a convenient and minimally invasive technique capable of dynamically representing the comprehensive tumor gene spectrum. This review systematically elaborates the clinical value of liquid biopsy as a breakthrough tool for precision diagnosis and treatment in breast cancer through dynamic detection of key biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and non-coding RNA (ncRNA). Specific genetic mutations and methylation signatures in ctDNA can be applied to early breast cancer screening, minimal residual disease monitoring, and tracking drug resistance mechanisms. CTCs enumeration (≥1/7.5 mL in early-stage cancer or ≥ 5/7.5 mL in metastatic cancer) and PD-L1 expression levels demonstrate direct correlations with prognostic stratification and the efficacy of immunotherapy. As the specificity and sensitivity of liquid biopsy continue to improve, personalized treatment strategies, informed by biomarker analysis and targeted precision therapies, have unveiled new avenues of hope for patients with breast cancer. However, several challenges persist in the practical application of liquid biopsy. Despite persistent challenges, such as insufficient standardization and difficulties in resolving low-abundance variants, future advancements should focus on multi-omics integration and AI-driven technological breakthroughs to overcome bottlenecks in clinical translation. This review summarizes cutting-edge liquid biopsy technologies for identifying clinically significant molecular biomarkers, focusing on discussing critical challenges in the strategies to advance precision oncology applications for optimized treatment guidance and disease surveillance in breast cancer.

PMID:40540857 | DOI:10.1016/j.ctrv.2025.102979

FAAP100:A biomarker based on pan-cancer analysis, promotes the progression of lung adenocarcinoma

Cell Signal. 2025 Jun 18;134:111950. doi: 10.1016/j.cellsig.2025.111950. Online ahead of print.

ABSTRACT

FAAP100 plays an essential role in DNA damage repair, with dysregulation associated with elevated cancer susceptibility. Nevertheless, comprehensive pan-cancer analyses examining FAAP100 prognostic significance, immune correlations, and epigenetic regulation remains unexplored. This study systematically characterized FAAP100 across 33 cancer types utilizing multi-omics data from TCGA, UALCAN, cBioPortal, TIMER2.0, and CPTAC. Analytical assessments included expression profiles, prognostic significance, and diagnostic utility, alongside associations with DNA methylation, immune cell infiltration, immune checkpoint gene expression, tumor mutational load (TMB), microsatellite instability (MSI), and drug resistance. Findings revealed significant FAAP100 upregulation across multiple cancer types, exhibiting inverse correlations to patient survival. Genomic characterization identified associations between FAAP100 overexpression and both copy number amplification and promoter hypomethylation. Immune profiling demonstrated robust correlations with immune cell infiltration levels and checkpoint molecule activity. Functional assays utilizing PC9 and H1299 cells indicated that FAAP100 enhances cellular proliferation and migration while inhibiting apoptosis processes. In vivo studies confirmed tumor growth suppression upon FAAP100 knockdown. Collectively, this multi-omics investigation identifies FAAP100 as a pan-cancer oncogene driver, highlighting its potential as both a prognostic biomarker and therapeutic target. The integrated analysis of expression patterns, epigenetic modifications, immune characteristics, and genomic alterations elucidates the mechanistic involvement of FAAP100 in tumor progression, providing a foundation for clinical application in precision oncology approaches..

PMID:40541815 | DOI:10.1016/j.cellsig.2025.111950

Comprehensive Bibliometric Analysis of Prediction Models for HCC: Current Trends and Future Prospects

J Gastrointest Cancer. 2025 Jun 19;56(1):139. doi: 10.1007/s12029-025-01249-1.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor, with rising incidence and mortality rates posing a significant threat to global public health. Accurate prediction of liver cancer occurrence and progression is essential for improving patient prognosis. This study uses bibliometric methods to analyze the current state and future trends in liver cancer prediction research.

METHODS: A search was conducted in the Web of Science (WOS) database on October 22, 2023, identifying 1092 articles on liver cancer prediction. These articles were quantitatively analyzed using CiteSpace 6.2 software, with a focus on research hotspots, authors, countries, and keywords.

RESULTS: The study involved 114 countries, 4254 institutions, and 280 journals, with 48,788 citations. China (826 papers) and the USA (96 papers) dominate the field. Leading institutions include Sun Yat-sen University, Fudan University, Zhejiang University, and Yonsei University. The most cited journals were Hepatology (2209 citations) and Journal of Hepatology (946 citations). Frontiers in Oncology had the highest H-index (14). Key authors include Kim Seung Up (23 papers) and Ahn Sang Hoon (H-index = 14). Early research focused on risk factors and staging, while recent studies emphasize DNA methylation, immune microenvironments, and tumor metastasis. Future research will focus on multi-omics data integration and AI-driven predictive model optimization.

CONCLUSION: This study provides a comprehensive overview of liver cancer prediction research, highlighting key trends and the potential of multi-omics data and machine learning to enhance predictive models and clinical outcomes.

PMID:40537718 | DOI:10.1007/s12029-025-01249-1

Biomarkers associated with cancer-related anorexia in lung cancer: a scoping review

Support Care Cancer. 2025 Jun 19;33(7):596. doi: 10.1007/s00520-025-09670-9.

ABSTRACT

PURPOSE: Anorexia is a frequent and serious symptom in patients with lung cancer, often leading to malnutrition and cachexia, and negatively affecting quality of life and survival. This scoping review systematically synthesizes current evidence on biomarkers associated with cancer-related anorexia (CRA) in lung cancer, aiming to clarify biological mechanisms and inform targeted interventions.

METHODS: We performed a comprehensive literature search of studies evaluating the associations between CRA and various biomarkers in patients with lung cancer. Data were extracted and analyzed for pathway, genomic, transcriptomic, epigenetic, proteomic, metabolic, and composite biomarkers.

RESULTS: A total of 33 studies were included, identifying more than 100 biomarkers closely associated with CRA in lung cancer. These include inflammatory cytokines, energy metabolism markers, epigenetic and transcriptomic alterations, and disruptions in multiple cellular signaling pathways. Our analysis demonstrates that CRA is not the result of a single factor but reflects widespread dysregulation across metabolic, immune, and signaling networks. Some studies suggest that nutritional and anti-inflammatory interventions, such as n-3 fatty acid and antioxidant supplementation, can modulate biomarker profiles and potentially improve clinical outcomes.

CONCLUSION: CRA in lung cancer is a multifactorial syndrome involving complex interactions among inflammatory, metabolic, and signaling pathways. Multi-omics biomarker integration holds promise for early detection and individualized treatment, but larger, multi-center studies are needed to confirm clinical utility and optimize management strategies. Precision interventions based on biomarker profiles should be further explored in future research and practice.

PMID:40536584 | DOI:10.1007/s00520-025-09670-9

MOLUNGN: a multi-omics graph neural network for biomarker discovery and accurate lung cancer classification

Front Genet. 2025 Jun 4;16:1610284. doi: 10.3389/fgene.2025.1610284. eCollection 2025.

ABSTRACT

INTRODUCTION: Lung cancer continues to pose significant global health burdens due to its high morbidity and mortality. This study aimed to systematically integrate biomedical datasets, particularly incorporating traditional Chinese medicine (TCM)-associated multi-omics data, employing advanced deep-learning methods enhanced by graph attention mechanisms. We sought to investigate molecular mechanisms underlying stage-wise lung cancer progression and identify pivotal stage-specific biomarkers to support precise cancer staging classification.

METHODS: We developed a novel multi-omics integrative model, named the Multi-Omics Lung Cancer Graph Network (MOLUNGN), based on Graph Attention Networks (GAT). Clinical datasets of non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), were analyzed to create omics-specific feature matrices comprising mRNA expression, miRNA mutation profiles, and DNA methylation data. MOLUNGN incorporated omics-specific GAT modules (OSGAT) combined with a Multi-Omics View Correlation Discovery Network (MOVCDN), effectively capturing intra- and inter-omics correlations. This framework enabled comprehensive classification of clinical cases into precise cancer stages, alongside the extraction of stage-specific biomarkers.

RESULTS: Evaluations utilizing publicly available datasets confirmed MOLUNGN's superior performance over existing methodologies. On the LUAD dataset, MOLUNGN achieved accuracy (ACC) of 0.84, Recall_weighted of 0.84, F1_weighted of 0.83, and F1_macro of 0.82. On the LUSC dataset, the model further improved, achieving ACC of 0.86, Recall_weighted of 0.86, F1_weighted of 0.85, and F1_macro of 0.84. Notably, critical stage-specific biomarkers with significant biological relevance to lung cancer progression were identified, facilitating robust gene-disease associations.

DISCUSSION: Our findings underscore the efficacy of MOLUNGN as an integrative framework in accurately classifying lung cancer stages and uncovering essential biomarkers. These biomarkers provide deep insights into lung cancer progression mechanisms and represent promising targets for future clinical validation. Integrating these biomarkers into the TCM-target-disease network enriches the understanding of TCM therapeutic potentials, laying a robust foundation for future precision medicine applications.

PMID:40534839 | PMC:PMC12174459 | DOI:10.3389/fgene.2025.1610284

  • ✇MIT Technology Review
  • The Download: tackling tech-facilitated abuse, and opening up AI hardware Charlotte Jee
    This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology. Why it’s so hard to stop tech-facilitated abuse After Gioia had her first child with her then husband, he installed baby monitors throughout their home—to “watch what we were doing,” she says, while he went to work. She’d turn them off; he’d get angry. By the time their third child turned seven, Gioia and her husband had divorced, but he still found ways
     

The Download: tackling tech-facilitated abuse, and opening up AI hardware

18 June 2025 at 20:15

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

Why it’s so hard to stop tech-facilitated abuse

After Gioia had her first child with her then husband, he installed baby monitors throughout their home—to “watch what we were doing,” she says, while he went to work. She’d turn them off; he’d get angry. By the time their third child turned seven, Gioia and her husband had divorced, but he still found ways to monitor her behavior. One Christmas, he gave their youngest a smartwatch. Gioia showed it to a tech-savvy friend, who found that the watch had a tracking feature turned on. It could be turned off only by the watch’s owner—her ex.

And Gioia is far from alone. In fact, tech-facilitated abuse now occurs in most cases of intimate partner violence—and we’re doing shockingly little to prevent it. Read the full story. 

—Jessica Klein 

This story is from the next print edition of MIT Technology Review, which explores power—who has it, and who wants it. It’s set to go live on Wednesday June 25, so subscribe & save 25% to read it and get a copy of the issue when it lands!

Why AI hardware needs to be open

—by Ayah Bdeir, a leader in the maker movement, champion of open source AI, and founder of littleBits, the hardware platform that teaches STEAM to kids through hands-on invention. 

Once again, the future of technology is being engineered in secret by a handful of people and delivered to the rest of us as a sealed, seamless, perfect device. When technology is designed like this, we are reduced to consumers. We don’t shape the tools; they shape us. 

However, this moment creates a chance to do things differently. Because away from the self-centeredness of Silicon Valley, a quiet, grounded sense of resistance is reactivating.  Read the full story.

MIT Technology Review Narrated: Deepfakes of your dead loved ones are a booming Chinese business

In China, people are seeking help from AI-generated avatars to process their grief after a family member passes away. Our story about this trend is the latest to be turned into a MIT Technology Review Narrated podcast, which we’re publishing each week on Spotify and Apple Podcasts. Just navigate to MIT Technology Review Narrated on either platform, and follow us to get all our new content as it’s released.

The must-reads

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.

1 Iran is going offline to avoid Israeli cyberattacks
A government spokesperson said it plans to disconnect completely from the global internet this evening. (The Verge)
+ How attacks on Iran’s oil exports could hurt China. (WSJ $)

2 Trump is giving TikTok another reprieve from a US ban
It’s been a full five years since he signed the original executive order telling Bytedance to sell it. (CNN)
+ Why Chinese manufacturers are going viral on TikTok. (MIT Technology Review)

3 Conspiracy theories about the Minnesota shooting are all over social media
Whenever there’s an information vacuum, people are all too keen to fill it with noise and nonsense. (NBC) 
+ The shooting suspect allegedly used data broker sites to find targets’ addresses. (Wired $)

4 Tensions between OpenAI and Microsoft are starting to boil over 
OpenAI has even threatened to report its formerly close partner to antitrust regulators. (WSJ $)
+ Here are the concessions OpenAI is seeking. (The Information $)
+ Inside the story that enraged OpenAI. (MIT Technology Review) 

5 California cops are using AI cameras to investigate ICE protests
And sharing license plate data with other agencies, a practice some experts say is illegal. (404 Media)
+ How a new type of AI is helping police skirt facial recognition bans. (MIT Technology Review)

6 Social media is now Americans’ primary news source
It’s overtaken TV for the first time. (Reuters)
+ They watched more TV via streaming than cable last month, too. (NYT $)

7 Weight loss drugs may not work quite as well as hoped
Researchers analysed data from 51,085 patients and found bariatric surgery delivered better, more sustainable results. (The Guardian)

8 What is AI doing to reading? 📖
Here’s what we stand to gain—and lose—when we outsource reading to machines. (New Yorker $) 

9 India is relying on China to build up its EV market
It’s taking a drastically different course to the US. (Rest of World)
+ Why EVs are (mostly) set for solid growth in 2025. (MIT Technology Review)

10 People are building AI tools to decipher cats’ meows 😸
Bet at least half of them are “feed me.” (Scientific American $)

Quote of the day

“Have we fallen so low? Have we no shame?”

—Remarks made by federal judge Williams G. Young this week as he voided some of the Trump administration’s cuts to National Institutes of Health grants, saying they were discriminatory, the New York Times reports. 

One more thing

a pixelated plate with the crusts of a sandwich and two pickle slices
STEPHANIE ARNETT/MIT TECHNOLOGY REVIEW | GETTY


Why AI could eat quantum computing’s lunch

Tech companies have been funneling billions of dollars into quantum computers for years. The hope is that they’ll be a game changer for fields as diverse as finance, drug discovery, and logistics.

But while the field struggles with the realities of tricky quantum hardware, another challenger is making headway in some of these most promising use cases. AI is now being applied to fundamental physics, chemistry, and materials science in a way that suggests quantum computing’s purported home turf might not be so safe after all. Read the full story.

—Edd Gent

We can still have nice things

A place for comfort, fun and distraction to brighten up your day. (Got any ideas? Drop me a line or skeet ’em at me.)

+ Wait a minute, Will Smith was offered a role in Inception? Much to think about.
+ No pain, no gain? Not necessarily.
+ John Waters, you really are one of a kind.
+ Say it ain’t so—I refuse to believe that young love is dead!

Mendelian randomization in cancer research: opportunities and challenges

Infect Agent Cancer. 2025 Jun 15;20(1):37. doi: 10.1186/s13027-025-00672-0.

ABSTRACT

Mendelian Randomization (MR) is increasingly used in cancer research to infer causal relationships by leveraging genetic variants as instrumental variables. While the growth of genome-wide association studies and biobank data has expanded the utility of MR, this surge-particularly pronounced in China-raises concerns about methodological rigor. The widespread adoption may be partly driven by the Chinese translation of key MR literature. Recent advances such as multivariable MR, mediation analysis, and integration with AI and omics data have enhanced the robustness and biological interpretability of MR studies. However, challenges persist, including horizontal pleiotropy, weak instrument bias, and misinterpretation of biomarkers as causal exposures. To improve MR study credibility, frameworks like STROBE-MR and MR-GRADE are being adopted. This article reviews methodological improvements and persistent pitfalls in MR, especially within cancer epidemiology, and highlights strategies for ensuring validity in this rapidly evolving field.

PMID:40518507 | PMC:PMC12168377 | DOI:10.1186/s13027-025-00672-0

A multi-phase approach using supervised algorithms and clinical models to generate high-accuracy signatures for pancreatic cancer

Comput Biol Med. 2025 Aug;194:110559. doi: 10.1016/j.compbiomed.2025.110559. Epub 2025 Jun 14.

ABSTRACT

BACKGROUND: The in silico analyses provide evidence supporting the potential of methylation-driven differentially expressed genes as therapeutic targets across cancer types. This leads us to identify novel targets and their associated drug compounds for further progress towards pancreatic cancer treatment.

OBJECTIVE: To identify targeted drugs based on methylation driven genes identified using bulk multi-omics data and single-cell level data to pinpoint important disease markers.

METHODS: The workflow involves screening using the TCGA and ICGC databases, followed by validation with GEO datasets. The study employs supervised learning algorithms like kNN and random forests, and constructs a prediction model using adaptive LASSO-Cox regression. The process also includes pathway analysis, evaluation of survival status, and immune profile deconvolution, as well as multistage evaluation of the methylation driven genes. We conducted drug targeting and molecular dynamic simulations, taking into account genes of interest.Lastly, molecular docking and dynamics simulations were used to find out if the key MEDEGs could be utilized as drug targets.

RESULTS: CD36, UGT1A1, TFF1, S100P, MUC13, CALHM3 and ANKRD44 were found to be top 7 methylation driven genes. The mutational profile was also documented along with pathway analysis, which showed concordance with our observation based on their significant enriched terms namely "Maintenance of Gastrointestinal Epithelium", and "Digestive System Homeostasis". CD36 had prognostic capabilities and was seen to significant in terms of survival and also showed significant immune dysregulation. Our novel findings suggest TFF1, S100P, and MUC13 were found to be associated with cell type specific expression as seen in single cell data and UGT1A1 was found to be suitable for probable drug targeting. CD36, UGT1A1, TFF1, S100P, and MUC13 showed concordance when observed at proteomics level and across other datasets. Apigenin-7-O-glucuronide emerged as the top binder for UDP-glucuronosyltransferase 1A1 (also known as UDP 1A1), forming stable complexes with favourable interactions. Catechin and epicatechin were identified as the best ligands for TFF1 and S100P, while rutin showed high-affinity binding to MUC13.

CONCLUSION: The study successfully identified and validated a panel of biomarkers specific to pancreatic cancer, with potential applications in early diagnosis and treatment. The findings highlight the importance of multi-omics data integration in cancer research and the potential of personalized medicine in improving patient outcomes. The in-silico drug targeting analysis provides a foundation for the development of novel drugs for PanCa treatment. Hence TFF1, S100P, MUC13, and UGT1A1 showcased themselves as most promising biomarkers and novel drug targets.

PMID:40517592 | DOI:10.1016/j.compbiomed.2025.110559

Advances in molecular pathology and therapy of non-small cell lung cancer

Signal Transduct Target Ther. 2025 Jun 15;10(1):186. doi: 10.1038/s41392-025-02243-6.

ABSTRACT

Over the past two decades, non-small cell lung cancer (NSCLC) has witnessed encouraging advancements in basic and clinical research. However, substantial unmet needs remain for patients worldwide, as drug resistance persists as an inevitable reality. Meanwhile, the journey towards amplifying the breadth and depth of the therapeutic effect requires comprehending and integrating diverse and profound progress. In this review, therefore, we aim to comprehensively present such progress that spans the various aspects of molecular pathology, encompassing elucidations of metastatic mechanisms, identification of therapeutic targets, and dissection of spatial omics. Additionally, we also highlight the numerous small molecule and antibody drugs, encompassing their application alone or in combination, across later-line, frontline, neoadjuvant or adjuvant settings. Then, we elaborate on drug resistance mechanisms, mainly involving targeted therapies and immunotherapies, revealed by our proposed theoretical models to clarify interactions between cancer cells and a variety of non-malignant cells, as well as almost all the biological regulatory pathways. Finally, we outline mechanistic perspectives to pursue innovative treatments of NSCLC, through leveraging artificial intelligence to incorporate the latest insights into the design of finely-tuned, biomarker-driven combination strategies. This review not only provides an overview of the various strategies of how to reshape available armamentarium, but also illustrates an example of clinical translation of how to develop novel targeted drugs, to revolutionize therapeutic landscape for NSCLC.

PMID:40517166 | PMC:PMC12167388 | DOI:10.1038/s41392-025-02243-6

A multi-omics and mediation-based genetic screening approach identifies STX4 as a key link between epigenetic regulation, immune cells, and childhood asthma

Childhood asthma presents a multifaceted immune-driven pathology shaped by genetic, epigenetic, and immune regulatory interactions. Despite extensive genome-wide analyses pinpointing multiple susceptibility lo...

Cancer gene identification from RNA variant allelic frequencies using RVdriver

Genome Biol. 2025 Jun 13;26(1):165. doi: 10.1186/s13059-025-03557-y.

ABSTRACT

Existing approaches to identifying cancer genes rely overwhelmingly on DNA sequencing data. Here, we introduce RVdriver, a computational tool that leverages paired bulk genomic and transcriptomic data to classify RNA variant allele frequencies (VAFs) of non-synonymous mutations relative to a synonymous mutation background. We analyze 7882 paired exomes and transcriptomes from 31 cancer types and identify novel, as well as known, cancer genes, complementing other DNA-based approaches. Furthermore, RNA VAFs of individual mutations are able to distinguish "driver" from "passenger" mutations within established cancer genes. This approach highlights the value of multi-omic approaches for cancer gene discovery.

PMID:40514689 | PMC:PMC12164115 | DOI:10.1186/s13059-025-03557-y

Integrative multi-omics profiling deciphers tumor microenvironment heterogeneity and immunotherapy vulnerabilities in lung neuroendocrine carcinomas

J Adv Res. 2025 Jun 11:S2090-1232(25)00427-8. doi: 10.1016/j.jare.2025.06.017. Online ahead of print.

ABSTRACT

INTRODUCTION: Lung neuroendocrine carcinomas (Lu-NECs) are rare, highly aggressive lung tumors with poor prognosis and limited therapeutic options. Understanding the tumor immune microenvironment (TIME) is crucial towards personalized therapeutic strategies.

OBJECTIVES: This study aims to systematically characterize the heterogeneity and complexity of the TIME in Lu-NECs by integrating proteomic, transcriptomic, and genomic data.

METHODS: We performed comprehensive immune-proteomic profiling of 76 Lu-NECs across diverse histopathological subtypes to elucidate intra-tumoral TIME heterogeneity at the proteomic level. Validation was conducted in multiple independent cohorts, including 112 Lu-NECs using immunohistochemistry, 147 Lu-NECs, and 17 small cell lung carcinoma samples using transcriptomics. We integrated proteomic, transcriptomic, genomic, and clinical data to assess molecular, immunological, and clinical features, as well as therapeutic vulnerabilities across different immune subtypes.

RESULTS: We delineated the immuno-proteomic landscape of Lu-NECs and identified two major immuno-proteomic clusters with distinct immunological, molecular, and clinical characteristics. IPC1 was characterized by high immune cell infiltration, while IPC2 exhibited sparse immune cell presence. Genomic analysis revealed distinct mutational patterns, with IPC1 showing a higher incidence of APOBEC-associated mutation signatures and IPC2 being enriched for mutations associated with defective DNA mismatch repair and tobacco-related mutagens. Functional analyses indicated that IPC1 was related to immune and oncogenic signaling activity, whereas IPC2 was associated with cancer stemness and proliferation-related features. Furthermore, IPC1 and IPC2 demonstrated histological subtype-specific clinical benefits from postoperative chemotherapy. Finally, we developed a machine learning model (iPROM) to predict Lu-NECs immune classification and improve risk stratification, which was validated across multiple independent cohorts.

CONCLUSIONS: This study advances the understanding of the tumor immune microenvironment in Lu-NECs through multi-omics characterization and highlights potential personalized therapeutic vulnerabilities tailored to the specific immune landscapes of Lu-NECs.

PMID:40513660 | DOI:10.1016/j.jare.2025.06.017

An organoid co-culture model for probing systemic anti-tumor immunity in lung cancer

Cell Stem Cell. 2025 Jun 6:S1934-5909(25)00191-2. doi: 10.1016/j.stem.2025.05.011. Online ahead of print.

ABSTRACT

Deciphering interactions between tumor micro- and systemic immune macroenvironments is essential for developing more effective cancer diagnosis and therapeutic strategies. Here, we established a gel-liquid interface (GLI) co-culture model of lung cancer organoids (LCOs) and paired peripheral-blood mononuclear cells (PBMCs), featuring enhanced interactions between immune cells and tumor organoids for optimized simulation of in vivo systemic anti-tumor immunity. By constructing a cohort of lung cancer patients, we demonstrated that the responses of GLI models under αPD1 treatment reflected the immunotherapy outcomes of the corresponding patients precisely. Furthermore, we dissected the various tumor immune processes mediated by PBMC-derived T cells within GLI models through functional multi-omics analyses, along with the characterization of circulating tumor-reactive T cells (GNLY+CD44+CD9+) with effector memory-like phenotypes as a potential indicator of immunotherapy efficacy. Our findings indicate that the GLI co-culture model can be used to develop diagnostic strategies for precision immunotherapies, as well as understanding the underlying mechanisms.

PMID:40513558 | DOI:10.1016/j.stem.2025.05.011

Improved tumor-type informed compared to tumor-informed mutation tracking for ctDNA detection and microscopic residual disease assessment in epithelial ovarian cancer

J Exp Clin Cancer Res. 2025 Jun 12;44(1):174. doi: 10.1186/s13046-025-03433-4.

ABSTRACT

BACKGROUND: Epithelial ovarian cancer (EOC) is a leading cause of cancer mortality in women, often diagnosed at advanced stages. While first-line treatments improve survival, relapses remain common, with 5-year survival rates below 40%. Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive EOC detection and monitoring. It may help assess treatment response, notably microscopic residual disease. Our objective was to compare two ctDNA characterization strategies in EOC for assessing tumor burden during first-line treatment: a tumor-informed approach based on somatic mutations and a tumor-type informed approach utilizing DNA methylation patterns.

METHODS: In the tumor-informed approach, whole exome sequencing (WES) was performed on EOC tumor DNA and matched PBMCs from 22 patients to identify tumor-specific mutations. Personalized panels were then designed to track these mutations in plasma cfDNA. In the tumor-type informed approach, differentially methylated loci (DMLs) were identified by comparing EOC samples, healthy ovarian tissues, and PBMCs. A unique custom methylation panel was designed, and a support vector machine classifier was trained to distinguish between methylation profiles in plasma cfDNA from healthy donors and from EOC patients. Plasma samples from 47 advanced-stage EOC patients receiving chemotherapy and 54 healthy subjects were analyzed.

RESULTS: For the tumor-informed approach, WES identified an average of 72 somatic mutations per patient. For the tumor-type informed approach, 52,173 DMLs were identified as tumor-specific markers. In 47 plasma samples tested by both approaches, ctDNA levels were significantly correlated (R = 0.56, p = 4.3 × 10-5), with 70.2% concordance in detection. At baseline, ctDNA was detected in 21/22 patients with the tumor-informed approach, and in 11/12 non-training baseline samples with the tumor-type-informed classifier. At end-of-treatment, the latter detected ctDNA in 16/22 samples, outperforming the former. Detection using this more sensitive approach was significantly associated with relapse (log-rank p = 0.009; hazard ratio = 9.44; 95% CI 1.22-73.26) and poorer overall survival (log-rank p = 0.041).

CONCLUSION: The tumor-type informed classifier demonstrated sensitivity and specificity for ctDNA detection, outperforming the tumor-informed approach in monitoring EOC progression. Requiring fewer sequencing data, it offers a practical, efficient solution for clinical management of EOC.

PMID:40506726 | PMC:PMC12160408 | DOI:10.1186/s13046-025-03433-4

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