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Minimal Residual Disease Detection: Implications for Clinical Diagnosis and Cancer Patient Treatment

MedComm (2020). 2025 May 15;6(6):e70193. doi: 10.1002/mco2.70193. eCollection 2025 Jun.

ABSTRACT

Minimal residual disease (MRD) serves as a pivotal biomarker for the clinical diagnosis and subsequent treatment of cancer patients. In hematological malignancies, MRD pose an increasingly serious threat to the health of Chinese people. Accurate MRD detection is essential for assessing relapse risk and optimizing therapeutic strategies, yet current methods such as flow cytometry, polymerase chain reaction (PCR), and next-generation sequencing (NGS) each have distinct limitations, and significant gaps remain in achieving optimal sensitivity and specificity of these technologies. This review provides a comprehensive analysis of MRD detection methods, high-lighting their clinical implications, including their roles in treatment decision-making, risk stratification, and patient outcomes. It discusses the strengths and weaknesses of existing techniques and explores emerging technologies that promise enhanced diagnostic precision. Key advancements such as integrating NGS with other methodologies and novel approaches like liquid biopsy and PCR are examined. The review underscores the academic and practical value of early and accurate MRD detection, emphasizing its impact on improving patient management and treatment outcomes. By addressing the limitations of current technologies and exploring future directions, this review aims to advance the field and support personalized medicine approaches to cancer treatment.

PMID:40384986 | PMC:PMC12079024 | DOI:10.1002/mco2.70193

Role of the "inflammation-immunity-metabolism" network in non-small cell lung cancer: a multi-omics analysis

21 May 2025 at 18:00

Discov Oncol. 2025 May 21;16(1):847. doi: 10.1007/s12672-025-02692-z.

ABSTRACT

Lung cancer remains one of the leading causes of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for 85% of cases worldwide. NSCLC pathogenesis and progression are intricately linked to inflammatory stimuli, immune evasion, and metabolic reprogramming. In this study, the impact of inflammation, immunity, and metabolism on NSCLC was investigated by a Mendelian randomization analysis taking 91 inflammatory factors, 731 immune cells, and 1400 metabolites as exposures, and the FinnGen database NSCLC cohort (ncases = 5315, ncontrol = 314,193) was the outcome. A number of metabolites, inflammatory proteins, and immune cells were identified as potentially associated with NSCLC based on mendelian randomization analysis. Validation in the UK Biobank database lung cancer cohort (ncases = 2671, ncontrols = 372,016) further confirmed the inhibitory role of the metabolite N-acetyl-aspartyl-glutamate (NAAG) on lung cancer. Subsequently, single-cell and protein-protein interaction analyses identified inflammatory protein expression patterns in NSCLC, distribution ratios of immune cells in NSCLC. Subsequent multi-omics network analysis showed key interaction nodes between NAAG and inflammatory proteins. These findings enhance the understanding of the roles of inflammation, immunity, and metabolism in NSCLC occurrence and progression, offering potential targets and strategies for further research on its treatment and management.

PMID:40397292 | PMC:PMC12095725 | DOI:10.1007/s12672-025-02692-z

  • ✇MIT Technology Review
  • Anthropic’s new hybrid AI model can work on tasks autonomously for hours at a time Rhiannon Williams
    Anthropic has announced two new AI models that it claims represent a major step toward making AI agents truly useful. AI agents trained on Claude Opus 4, the company’s most powerful model to date, raise the bar for what such systems are capable of by tackling difficult tasks over extended periods of time and responding more usefully to user instructions, the company says. Claude Opus 4 has been built to execute complex tasks that involve completing thousands of steps over several hours. Fo
     

Anthropic’s new hybrid AI model can work on tasks autonomously for hours at a time

23 May 2025 at 00:51

Anthropic has announced two new AI models that it claims represent a major step toward making AI agents truly useful.

AI agents trained on Claude Opus 4, the company’s most powerful model to date, raise the bar for what such systems are capable of by tackling difficult tasks over extended periods of time and responding more usefully to user instructions, the company says.

Claude Opus 4 has been built to execute complex tasks that involve completing thousands of steps over several hours. For example, it created a guide for the video game Pokémon Red while playing it for more than 24 hours straight. The company’s previously most powerful model, Claude 3.7 Sonnet, was capable of playing for just 45 minutes, says Dianne Penn, product lead for research at Anthropic.

Similarly, the company says that one of its customers, the Japanese technology company Rakuten, recently deployed Claude Opus 4 to code autonomously for close to seven hours on a complicated open-source project. 

Anthropic achieved these advances by improving the model’s ability to create and maintain “memory files” to store key information. This enhanced ability to “remember” makes the model better at completing longer tasks.

“We see this model generation leap as going from an assistant to a true agent,” says Penn. “While you still have to give a lot of real-time feedback and make all of the key decisions for AI assistants, an agent can make those key decisions itself. It allows humans to act more like a delegator or a judge, rather than having to hold these systems’ hands through every step.”

While Claude Opus 4 will be limited to paying Anthropic customers, a second model, Claude Sonnet 4, will be available for both paid and free tiers of users. Opus 4 is being marketed as a powerful, large model for complex challenges, while Sonnet 4 is described as a smart, efficient model for everyday use.  

Both of the new models are hybrid, meaning they can offer a swift reply or a deeper, more reasoned response depending on the nature of a request. While they calculate a response, both models can search the web or use other tools to improve their output.

AI companies are currently locked in a race to create truly useful AI agents that are able to plan, reason, and execute complex tasks both reliably and free from human supervision, says Stefano Albrecht, director of AI at the startup DeepFlow and coauthor of Multi-Agent Reinforcement Learning: Foundations and Modern Approaches. Often this involves autonomously using the internet or other tools. There are still safety and security obstacles to overcome. AI agents powered by large language models can act erratically and perform unintended actions—which becomes even more of a problem when they’re trusted to act without human supervision.

“The more agents are able to go ahead and do something over extended periods of time, the more helpful they will be, if I have to intervene less and less,” he says. “The new models’ ability to use tools in parallel is interesting—that could save some time along the way, so that’s going to be useful.”

As an example of the sorts of safety issues AI companies are still tackling, agents can end up taking unexpected shortcuts or exploiting loopholes to reach the goals they’ve been given. For example, they might book every seat on a plane to ensure that their user gets a seat, or resort to creative cheating to win a chess game. Anthropic says it managed to reduce this behavior, known as reward hacking, in both new models by 65% relative to Claude Sonnet 3.7. It achieved this by more closely monitoring problematic behaviors during training, and improving both the AI’s training environment and the evaluation methods.

  • ✇MIT Technology Review
  • By putting AI into everything, Google wants to make it invisible  Will Douglas Heaven
    If you want to know where AI is headed, this year’s Google I/O has you covered. The company’s annual showcase of next-gen products, which kicked off yesterday, has all of the pomp and pizzazz, the sizzle reels and celebrity walk-ons, that you’d expect from a multimillion-dollar marketing event. But it also shows us just how fast this still experimental technology is being subsumed into a lineup designed to sell phones and subscription tiers. Never before have I seen this thing we call artific
     

By putting AI into everything, Google wants to make it invisible 

If you want to know where AI is headed, this year’s Google I/O has you covered. The company’s annual showcase of next-gen products, which kicked off yesterday, has all of the pomp and pizzazz, the sizzle reels and celebrity walk-ons, that you’d expect from a multimillion-dollar marketing event.

But it also shows us just how fast this still experimental technology is being subsumed into a lineup designed to sell phones and subscription tiers. Never before have I seen this thing we call artificial intelligence appear so normal.

Yes, Google’s roster of consumer-facing products is the slickest on offer. The firm is bundling most of its multimodal models into its Gemini app, including the new Imagen 4 image generator and the new Veo 3 video generator. That means you can now access Google’s full range of generative models via a single chatbot. It also announced Gemini Live, a feature that lets you share your phone’s screen or your camera’s view with the chatbot and ask it about what it can see.

Those features were previously only seen in demos of Project Astra, a “universal AI assistant“ that Google DeepMind is working on. Now, Google is inching toward putting Project Astra into the hands of anyone with a smartphone.

Google is also rolling out AI Mode, an LLM-powered front end to search. This can now pull in personal information from Gmail or Google Docs to tailor searches to users. It will include Deep Search, which can break a query down into hundreds of individual searches and then summarize the results; a version of Project Mariner, Google DeepMind’s browser-using agent; and Search Live, which lets you hold up your camera and ask it what it sees.

This is the new frontier. It’s no longer about who has the most powerful models, but who can spin them into the best products. OpenAI’s ChatGPT includes many similar features to Gemini’s. But with its existing ecosystem of consumer services and billions of existing users, Google has a clear advantage. Power users wanting access to the latest versions of everything on display can now sign up for Google AI Ultra for $250 a month.  

When OpenAI released ChatGPT in late 2022, Google was caught on the back foot and was forced to jump into higher gear to catch up. With this year’s product lineup, it looks as if Google has stuck its landing.

On a preview call, CEO Sundar Pichai claimed that AI Overviews, a precursor to AI Mode that provides LLM-generated summaries of search results, had turned out to be popular with hundreds of millions of users. He speculated that many of them may not even know (or care) that they were using AI—it was just a cool new way to search. Google I/O gives a broader glimpse of that future, one where AI is invisible.

“More intelligence is available, for everyone, everywhere,” Pichai told his audience. I think we are expected to marvel. But by putting AI in everything, Google is turning AI into a technology we won’t notice and may not even bother to name.

Cells keep diverse company in diseased tissues

Cancer Res. 2025 May 16. doi: 10.1158/0008-5472.CAN-25-2070. Online ahead of print.

ABSTRACT

Emerging spatial profiling technologies have revolutionized our understanding of how tissue architecture shapes disease progression, yet the contribution of cellular diversity remains underexplored. Here, Ding and colleagues introduce multiomics and ecological spatial analysis (MESA), an ecology-inspired framework that integrates spatial and single-cell expression data to quantify tissue diversity across multiple scales. MESA both identifies distinct cellular neighborhoods and computes a variety of diversity metrics alongside the identification of diversity "hotspots". Applied to human tonsil tissue, MESA revealed previously undetected germinal center organization, while in spleen tissue of a murine lupus model, MESA highlights increasing cellular diversity with disease progression. Importantly, diversity hotspots do not correspond to conventional compartments identified by existing methods, presenting an orthogonal metric of spatial organization. In colorectal cancer, MESA's diversity metrics outperformed established subtypes at predicting patient survival, while in hepatocellular carcinoma, multi-omic integration identified significantly more ligand-receptor interactions between immune cells compared to single-modality analysis. This work establishes cellular diversity within tissues as a critical correlate of disease progression and underscores the value of multi-omic integration in spatial biology.

PMID:40378285 | DOI:10.1158/0008-5472.CAN-25-2070

Application of artificial intelligence and machine learning in lung transplantation: a comprehensive review

Front Digit Health. 2025 May 1;7:1583490. doi: 10.3389/fdgth.2025.1583490. eCollection 2025.

ABSTRACT

Lung transplantation (LTx) is an effective method for treating end-stage lung disease. The management of lung transplant recipients is a complex, multi-stage process that involves preoperative, intraoperative, and postoperative phases, integrating multidimensional data such as demographics, clinical data, pathology, imaging, and omics. Artificial intelligence (AI) and machine learning (ML) excel in handling such complex data and contribute to preoperative assessment and postoperative management of LTx, including the optimization of organ allocation, assessment of donor suitability, prediction of patient and graft survival, evaluation of quality of life, and early identification of complications, thereby enhancing the personalization of clinical decision-making. However, these technologies face numerous challenges in real-world clinical applications, such as the quality and reliability of datasets, model interpretability, physicians' trust in the technology, and legal and ethical issues. These problems require further research and resolution so that AI and ML can more effectively enhance the success rate of LTx and improve patients' quality of life.

PMID:40376618 | PMC:PMC12078212 | DOI:10.3389/fdgth.2025.1583490

Solid phase transitions as a solution to the genome folding paradox

Nature, Published online: 14 May 2025; doi:10.1038/s41586-025-09043-6

In vitro reconstitution and in vivo live-cell imaging of LHX2–EBF1–LDB1 enhancer hubs in olfactory sensory neurons reveals that these transcription factors form condensates with solid, rather than liquid, phase properties.

Tumor-derived exosomal CCT6A serves as a matchmaker introducing chemokines to tumor-associated macrophages in pancreatic ductal adenocarcinoma

Cell Death Dis. 2025 May 15;16(1):382. doi: 10.1038/s41419-025-07720-y.

ABSTRACT

M2-polarized tumor-associated macrophages (TAMs) are a key factor contributing to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). While various factors within the tumor microenvironment (TME) drive their formation, the role of PDAC-derived exosomes in this process remains unclear. We aim to clarify the regulatory impacts of tumor-derived exosomes to TAMs. After the intratumoral injection to subcutaneous tumor of C57BL/6 mice, we demonstrated PDAC-derived exosomes exacerbate PDAC progression, accompanied with upregulated M2 phenotype of TAMs and unaffected proliferation signatures. Through intratumoral injection model and multi-Omics analyses, we identified CCT6A as a novel tumor-derived exosomal protein, bridging TAMs M2 polarization and PDAC prognosis. Co-culture with exosomes derived from CCT6Ahigh PDAC leads to greater M2 phenotype of TAMs via PI3K-AKT signaling. According to proteomics data, chemokines' abundance reduces over tenfold once exosomal CCT6A absence, including CXCL1, CXCL3, CCL20 and CCL5, whose interaction with CCT6A in PDAC cells was confirmed by interactomics data. Moreover, we found silencing CCT6A abrogated the antagonism effects of CD47 antibody immunotherapy. Our findings implied that the subunit of the T-complex protein Ring Complex (TRiC) CCT6A serves as a matchmaker during exosome-mediated chemokines transfer from PDAC to TAMs. Silencing CCT6A effectively sensitized PDAC to CD47 antibody immunotherapy in vivo.

PMID:40374617 | PMC:PMC12081750 | DOI:10.1038/s41419-025-07720-y

  • ✇MRD
  • Biomarkers in adjuvant and neoadjuvant treatment of melanoma Julian Kött · Christoffer Gebhardt
    Dermatologie (Heidelb). 2025 Jun;76(6):361-364. doi: 10.1007/s00105-025-05506-z. Epub 2025 May 7.ABSTRACTBACKGROUND: Personalized treatment of melanoma is becoming increasingly more important. Biomarkers offer the possibility of controlling treatment more precisely and reducing side effects.OBJECTIVE: The aim of this text is to provide an overview of current tissue-based, blood-based and radiological biomarkers and their clinical application in melanomas.MATERIAL AND METHODS: A literature resear
     

Biomarkers in adjuvant and neoadjuvant treatment of melanoma

7 May 2025 at 18:00

Dermatologie (Heidelb). 2025 Jun;76(6):361-364. doi: 10.1007/s00105-025-05506-z. Epub 2025 May 7.

ABSTRACT

BACKGROUND: Personalized treatment of melanoma is becoming increasingly more important. Biomarkers offer the possibility of controlling treatment more precisely and reducing side effects.

OBJECTIVE: The aim of this text is to provide an overview of current tissue-based, blood-based and radiological biomarkers and their clinical application in melanomas.

MATERIAL AND METHODS: A literature research and analysis of current studies on biomarkers in adjuvant and neoadjuvant treatment of melanomas were carried out and relevant congress contributions were additionally included.

RESULTS: Tissue-based programmed cell death 1 ligand 1 (PD-L1) expression, interferon gamma (IFNγ) signature, gene expression profiles (GEP) and tumor mutational burden (TMB) are of prognostic and predictive relevance. Blood-based circulating tumor DNA (ctDNA) in the sense of a liquid biopsy should be emphasized as a personalized biomarker for longitudinal tracking during treatment or aftercare. Positron emission tomography computed tomography (PET-CT) and body composition enable an improved assessment of treatment efficiency. There are currently no data from prospective validation studies on these biomarkers; initial data from the NivoMela study are awaited.

CONCLUSION: The combination of tissue-based, blood-based and radiological biomarkers in terms of multiparametric approaches is promising but further prospective validation is needed for broad clinical use. These are currently not comprehensively implemented in the clinical routine in centers or in remuneration procedures.

PMID:40335648 | DOI:10.1007/s00105-025-05506-z

Emerging biomarkers for pancreatic cancer: from early detection to personalized therapy

Clin Transl Oncol. 2025 May 10. doi: 10.1007/s12094-025-03947-5. Online ahead of print.

ABSTRACT

Pancreatic cancer (PC) remains one of the most lethal malignancies, primarily due to its poor prognosis and late diagnosis. Biomarkers are essential in enhancing diagnostic accuracy, prognostic assessments, and therapeutic strategies, thereby addressing these challenges. Conventional biomarkers, such as CA 19-9, are widely used for monitoring disease progression but have limitations in early detection and specificity, necessitating complementary markers like CEA and MUC1. Emerging genetic biomarkers, including KRAS mutations and TP53 alterations, offer critical insights into tumorigenesis and serve as valuable diagnostic, prognostic, and therapeutic targets. Epigenetic biomarkers, such as DNA methylation and histone modifications, provide additional molecular layers, with aberrant methylation patterns and dysregulated histone modifications influencing tumor aggressiveness and therapy resistance. RNA-based biomarkers, particularly microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), play pivotal roles in regulating tumor biology and offer significant diagnostic and therapeutic potential. Protein-based biomarkers, including glycoproteins and cytokines, alongside liquid biopsy components like circulating tumor DNA (ctDNA), exosomes, and circulating tumor cells (CTCs), facilitate real-time disease monitoring and early detection. Personalized therapy is increasingly guided by these biomarkers, which predict responses to chemotherapy and immunotherapy. Despite challenges in biomarker validation and clinical implementation, advancements in multi-omics, artificial intelligence, and collaborative research hold promise for improving patient outcomes and survival rates in PC.

PMID:40348906 | DOI:10.1007/s12094-025-03947-5

Article: Best Practices to Build Energy-Efficient AI/ML Systems

9 May 2025 at 19:00

In this article, author Lakshmithejaswi Narasannagari discusses the sustainable innovations in AI/ML technologies, how to track carbon footprint in all stages of ML systems lifecycle and best practices for model development and deployment.

By Lakshmithejaswi Narasannagari

Decoding per- and polyfluoroalkyl substances (PFAS) in hepatocellular carcinoma: a multi-omics and computational toxicology approach

J Transl Med. 2025 May 2;23(1):504. doi: 10.1186/s12967-025-06517-z.

ABSTRACT

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are synthetic chemicals known for their widespread use and environmental persistence. These compounds have been increasingly linked to hepatotoxicity and the development of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which PFAS contribute to HCC remain underexplored.

METHODS: This study employs a multi-omics approach that combines network toxicology, integrated machine learning, single-cell RNA sequencing, spatial transcriptomics, experimental validation, and molecular docking simulations to uncover the mechanisms through which PFAS exposure drives HCC. We analyzed publicly available transcriptomic data from several HCC cohorts and used differential gene expression analysis to identify targets associated with both PFAS exposure and HCC. We constructed a protein-protein interaction (PPI) network and a survival risk model, the PFAS-related HCC signature (PFASRHSig), based on integrated machine learning to identify prognostic biomarkers, with the goal of identifying core targets of PFAS in HCC progression and prognosis. RT-qPCR and immunohistochemical (IHC) staining were used to validate the expression levels of the targets in both tumor and normal tissues. Molecular docking simulations were conducted to assess the binding affinities between PFAS compounds and selected target proteins.

RESULTS: Functional enrichment studies revealed that PFAS targets were associated with metabolic signaling pathways, which are actively involved in lipid, glucose, drug metabolism, etc. Through integrated machine learning and PPI network analysis, we identified six genes, APOA1, ESR1, IGF1, PPARGC1A, SERPINE1, and PON1, that serve as core targets of PFAS in both HCC progression and prognosis. These targets were further validated via bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomics, which revealed differential expression patterns across various cell types in the HCC tumor microenvironment. The results of RT-qPCR and IHC staining were consistent with the in silico findings. Molecular docking simulations revealed strong binding affinities between PFAS compounds and these core targets, supporting their potential roles in PFAS-induced hepatocarcinogenesis.

CONCLUSIONS: Our study highlights key molecular targets and pathways involved in PFAS-induced liver carcinogenesis and proposes a robust survival risk model (PFASRHSig) for HCC. These findings provide new insights into PFAS toxicity mechanisms and offer potential therapeutic targets for mitigating the health risks associated with PFAS exposure. Collectively, our findings help in advancing clinical applications by providing insights into disease mechanisms and potential therapeutic interventions.

PMID:40317014 | PMC:PMC12049027 | DOI:10.1186/s12967-025-06517-z

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