Liquid biopsy technologies for noninvasive disease detection and monitoring using blood and other biofluids

Circulating Tumor DNA (ctDNA) and Cancer Detection

Recent studies have highlighted the potential of circulating tumor DNA (ctDNA) as a biomarker for early cancer detection and monitoring treatment response. One significant study evaluated the multicancer early detection (MCED) test, which utilizes genetic and fragmentomics-based features from plasma cell-free DNA. This test demonstrated strong potential for improving early cancer detection, suggesting that ctDNA analysis could enhance clinical decision-making (ref: Bao doi.org/10.1038/s41591-025-03735-2/). Another study focused on pancreatic cancer, where a cell-free DNA fragmentomics-based model achieved an impressive area under the curve (AUC) of 0.992 in training and 0.987 in validation datasets, indicating high accuracy in distinguishing pancreatic ductal adenocarcinoma (PDAC) from controls (ref: Yin doi.org/10.1200/JCO.24.00287/). Furthermore, ctDNA was detectable up to three years prior to clinical diagnosis in a cohort study, providing critical benchmarks for early detection sensitivity (ref: Wang doi.org/10.1158/2159-8290.CD-25-0375/). These findings collectively underscore the transformative potential of ctDNA in cancer diagnostics, particularly for early-stage detection and monitoring therapeutic efficacy. In the context of specific cancers, a study on metastatic prostate cancer analyzed ctDNA from patients undergoing treatment with lutetium-177-PSMA-617 versus cabazitaxel, revealing insights into predictive genomic biomarkers (ref: Kwan doi.org/10.1038/s41591-025-03704-9/). Additionally, urine tumor DNA was shown to stratify recurrence risk in patients treated for non-muscle-invasive bladder cancer, with significant differences in event-free survival based on UroAmp positivity (ref: St-Laurent doi.org/10.1016/j.eururo.2025.03.023/). These studies illustrate the diverse applications of ctDNA in various cancer types, emphasizing its role in enhancing patient management and treatment outcomes.

Liquid Biopsy Technologies and Methodologies

Liquid biopsy technologies are rapidly evolving, offering innovative methodologies for cancer diagnosis and monitoring. A notable advancement is the development of a 'label-capture-release' process for isolating viable circulating tumor cells (CTCs), which addresses the challenges of heterogeneity in CTC populations (ref: Lao doi.org/10.1016/j.xinn.2025.100805/). This technique enhances the efficiency of CTC enrichment from clinical samples, paving the way for real-time drug susceptibility testing. Another study introduced a novel microchip-based exosome analysis system, achieving an exosome isolation efficiency of 90.4% through a vessel-like microtunnel design, which significantly improves separation and detection performance compared to traditional methods (ref: Xu doi.org/10.1002/smll.202502763/). Moreover, the integration of artificial intelligence in analyzing cell-free oncRNA biomarkers has shown promise for early-stage colorectal cancer detection, demonstrating high clinical performance in a cohort study (ref: Momen-Roknabadi doi.org/10.1158/1078-0432.CCR-25-0449/). Additionally, a study on the VISION trial explored the efficacy of liquid versus tissue biopsies for detecting MET exon 14 skipping in non-small cell lung cancer, revealing that ctDNA burden correlates with patient outcomes (ref: Rolfo doi.org/10.1158/1078-0432.CCR-24-4097/). These advancements in liquid biopsy methodologies not only enhance diagnostic accuracy but also facilitate personalized treatment approaches, underscoring their potential impact on cancer management.

Tumor Microenvironment and Immunotherapy

The tumor microenvironment (TME) plays a crucial role in shaping the efficacy of immunotherapy, with recent studies revealing intricate interactions between tumor cells and immune components. One study introduced a novel nanoinducer that selectively induces type-II immunogenic cell death through endoplasmic reticulum stress, enhancing tumor immunogenicity and response to immunotherapy (ref: Zhang doi.org/10.1002/adma.202501953/). This approach highlights the potential of targeting specific cellular pathways to improve therapeutic outcomes in cancer treatment. Additionally, a multi-threshold micelle engineered to activate the STING pathway demonstrated improved tumor accumulation and enhanced immune signaling, suggesting that optimizing drug delivery systems can significantly bolster the effectiveness of immunotherapies (ref: Bennett doi.org/10.1021/jacs.4c17082/). In the context of ovarian cancer, distinct PD-L1 expression patterns across tissue types were associated with varying tumor microenvironments, impacting the predictive value of PD-L1 for response to pembrolizumab (ref: Collet doi.org/10.1158/1078-0432.CCR-24-2712/). Furthermore, research on HHLA2 in hepatocellular carcinoma indicated its potential as a biomarker for stratifying patients for targeted therapy, emphasizing the importance of understanding the TME in developing personalized treatment strategies (ref: Huang doi.org/10.1186/s13046-025-03407-6/). These findings collectively underscore the critical role of the TME in influencing immunotherapy outcomes and the need for innovative strategies to manipulate these interactions for enhanced therapeutic efficacy.

Cancer Genomics and Biomarkers

Cancer genomics continues to advance our understanding of tumor biology and the development of targeted therapies. A comprehensive mutational analysis of the cricket paralysis virus internal ribosome entry site utilized next-generation sequencing to explore the sequence-function relationship, providing insights into RNA translation mechanisms (ref: Grunseich doi.org/10.1093/nar/). This study exemplifies the utility of genomic tools in elucidating fundamental biological processes that can inform therapeutic strategies. In the realm of cancer of unknown primary (CUP), whole genome sequencing (WGTS) was shown to surpass panel testing in diagnostic accuracy, detecting additional mutations relevant for treatment in 76% of cases (ref: Rebello doi.org/10.1038/s41467-025-59661-x/). This highlights the importance of comprehensive genomic profiling in guiding precision medicine. Furthermore, the modeling of population-level impacts of cell-free DNA screening for colorectal cancer in Canada revealed significant potential for improving clinical and economic outcomes compared to traditional screening methods (ref: Hutchinson doi.org/10.1001/jamaoncol.2025.0908/). These studies collectively emphasize the transformative potential of genomics in cancer diagnosis, treatment selection, and the development of personalized therapeutic approaches.

Early Cancer Detection and Screening

Early cancer detection remains a critical focus in oncology, with innovative approaches being developed to enhance screening methodologies. One study demonstrated the ultrasensitive detection of circulating multiple myeloma cells using next-generation flow after immunomagnetic enrichment, achieving a positive predictive value of 95.1% (ref: Lasa doi.org/10.1182/blood.2025029234/). This advancement underscores the potential for liquid biopsies to provide timely insights into tumor dynamics and patient management. Additionally, the application of artificial intelligence in analyzing cell-free oncRNA biomarkers has shown promise for the early detection of colorectal cancer, achieving high sensitivity and specificity in validation cohorts (ref: Momen-Roknabadi doi.org/10.1158/1078-0432.CCR-25-0449/). Furthermore, a study investigating PD-L1 expression across different tissue types in ovarian cancer revealed distinct patterns that could influence treatment response, highlighting the importance of understanding tumor biology in screening efforts (ref: Collet doi.org/10.1158/1078-0432.CCR-24-2712/). These findings collectively emphasize the critical role of early detection in improving treatment outcomes and the need for continued innovation in screening technologies.

Therapeutic Monitoring and Treatment Response

Therapeutic monitoring and understanding treatment response are essential for optimizing cancer care. Recent studies have focused on identifying biomarkers that can predict patient outcomes and guide therapy decisions. For instance, HHLA2 expression was found to correlate with c-Met activation in hepatocellular carcinoma, serving as a potential liquid biopsy marker for targeted therapy (ref: Huang doi.org/10.1186/s13046-025-03407-6/). This highlights the importance of identifying reliable biomarkers for stratifying patients based on their likelihood of benefiting from specific treatments. Moreover, the antitumor activity of rucaparib combined with PLX038A in serous endometrial carcinoma was evaluated using patient-derived xenografts, demonstrating the potential of novel drug combinations to improve outcomes in challenging cancer subtypes (ref: Hou doi.org/10.1186/s13046-025-03406-7/). Additionally, macrophage responses to bexmarilimab were shown to be influenced by the tumor microenvironment, indicating that local conditions can significantly affect therapeutic efficacy (ref: Rannikko doi.org/10.1136/jitc-2024-011292/). These studies collectively underscore the need for personalized approaches in therapeutic monitoring and the importance of understanding the biological context of treatment responses.

Extracellular Vesicles and RNA Profiling

Extracellular vesicles (EVs) and RNA profiling are emerging as pivotal components in cancer diagnostics and monitoring. A comprehensive workflow integrating mass spectrometry and ELISA-based validation was developed to identify EV protein biomarkers for colorectal cancer, addressing the need for reliable non-invasive diagnostic tools (ref: Wang doi.org/10.1016/j.xcrm.2025.102090/). This approach underscores the potential of EVs in liquid biopsy applications, facilitating early detection and monitoring of cancer progression. Additionally, a study on the hepatotoxicity induced by Zearalenone explored the role of exosome-encapsulated miRNA let-7d-3p, revealing insights into the mechanisms of liver injury and the potential for using exosomal RNA as biomarkers for toxicity (ref: Xu doi.org/10.1016/j.jhazmat.2025.138737/). Furthermore, the development of innovative drug delivery systems, such as pH-sensitive nanoparticles for co-delivery of anti-PD-1 antibodies and MDK-siRNA, highlights the intersection of EV research with therapeutic strategies aimed at overcoming immune checkpoint blockade resistance (ref: Xu doi.org/10.1186/s13046-025-03396-6/). These findings collectively emphasize the significance of EVs and RNA profiling in enhancing cancer diagnostics and therapeutic monitoring.

Innovative Drug Delivery Systems

Innovative drug delivery systems are crucial for enhancing the efficacy of cancer therapies while minimizing side effects. Recent advancements include the development of vessel-like microtunnels integrated with biomimetic octopus tentacles for efficient exosome isolation, achieving an impressive 90.4% isolation efficiency (ref: Xu doi.org/10.1002/smll.202502763/). This novel approach not only improves the detection of cancer biomarkers but also facilitates the monitoring of treatment responses through liquid biopsies. Additionally, a study introduced a pH-sensitive nanoparticle system designed for the concurrent delivery of anti-PD-1 antibodies and MDK-siRNA, effectively reshaping the immunosuppressive tumor microenvironment and overcoming resistance to immune checkpoint inhibitors (ref: Xu doi.org/10.1186/s13046-025-03396-6/). Furthermore, stable intermolecular charge-transfer nanocrystals have been explored as immunogenic cell death adjuvants for photoimmunotherapy, showcasing the potential of organic photothermal agents in precision cancer treatment (ref: Gao doi.org/10.1016/j.biomaterials.2025.123436/). These innovations highlight the ongoing efforts to refine drug delivery systems, ultimately aiming to enhance therapeutic outcomes and patient quality of life.

Key Highlights

Disclaimer: This is an AI-generated summarization. Please refer to the cited articles before making any clinical or scientific decisions.