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

Circulating Tumor DNA and Biomarkers

Circulating tumor DNA (ctDNA) has emerged as a critical biomarker in various malignancies, providing insights into disease progression and treatment response. In large B-cell lymphoma, a study demonstrated that 55% and 78% of patients achieved undetectable ctDNA after two cycles and at the end of therapy, respectively, with a notable difference in progression-free survival (PFS) between detectable (67%) and undetectable ctDNA (96%) after two cycles (ref: Roschewski doi.org/10.1200/JCO-25-01534/). Similarly, in metastatic colorectal cancer, ctDNA analysis revealed that patients with wild-type RAS/BRAF had significantly longer median PFS (3.3 vs 1.9 months) and overall survival (7.9 vs 4.9 months) compared to those with mutations, highlighting the prognostic value of ctDNA in guiding therapy (ref: Zaanan doi.org/10.1093/jnci/). Furthermore, a systematic review and meta-analysis encompassing 56 studies with 3735 patients confirmed the prognostic significance of sequential liquid biopsies in metastatic colorectal cancer, emphasizing ctDNA's role in monitoring treatment efficacy (ref: Holz doi.org/10.1016/j.ctrv.2025.102999/). These findings collectively underscore the potential of ctDNA as a non-invasive biomarker for assessing treatment response and predicting outcomes across various cancers, including renal cell carcinoma and rectal cancer, where ctDNA's predictive capabilities were also explored (ref: Akiyoshi doi.org/10.1158/1078-0432.CCR-25-1242/; Rini doi.org/10.1016/j.annonc.2025.08.007/).

Liquid Biopsy Technologies

Liquid biopsy technologies are revolutionizing cancer diagnostics and monitoring by providing non-invasive methods to analyze tumor-derived materials. A comprehensive review highlighted the importance of preanalytical variables in liquid biopsy for brain tumors, emphasizing that factors such as sample collection and handling significantly impact the reliability of results (ref: Bettegowda doi.org/10.1093/neuonc/). In acute myeloid leukemia, a study utilizing plasma metabolomic and lipidomic analyses of 231 samples revealed that specific lipid levels could predict chemotherapy response and survival, indicating the potential of metabolic profiling in guiding treatment decisions (ref: O'Brien doi.org/10.1182/blood.2025029132/). Additionally, the development of a novel magnetic nanochains platform for N-glycoproteomic analysis of extracellular vesicles addresses the challenges of low abundance in biofluids, enhancing the detection and characterization of tumor markers (ref: Li doi.org/10.1038/s41467-025-63075-0/). These advancements in liquid biopsy technologies not only improve diagnostic accuracy but also facilitate personalized treatment approaches by enabling real-time monitoring of tumor dynamics.

Cancer Immunotherapy

Cancer immunotherapy continues to evolve, with recent studies exploring innovative strategies to enhance treatment efficacy. One study identified the probiotic Clostridium butyricum as a potential enhancer of anti-PD-1 therapy in colorectal cancer, demonstrating improved tumor suppression in models with microsatellite instability (ref: Xie doi.org/10.1016/j.ccell.2025.07.012/). Another approach involved the use of a bioinspired ruthenium-manganese-oxygen complex designed for biocatalytic and radiosensitization therapies, which showed promise in eradicating both primary and metastatic tumors by enhancing immune responses (ref: Li doi.org/10.1038/s41467-025-62999-x/). Furthermore, the combination of pembrolizumab with radiotherapy in high-risk localized sarcoma patients led to a significant improvement in disease-free survival, highlighting the synergistic effects of immunotherapy and traditional modalities (ref: Sobti doi.org/10.1136/jitc-2025-012053/). These findings underscore the potential of integrating immunotherapy with other treatment modalities to overcome resistance and improve patient outcomes.

Tumor Microenvironment and Metastasis

The tumor microenvironment plays a crucial role in cancer progression and metastasis, with recent studies elucidating its complex interactions. Research demonstrated that gut microbiota-mediated bile acid metabolism significantly influences colorectal cancer liver metastasis by altering neutrophil recruitment, suggesting that microbial composition could be a therapeutic target (ref: Zheng doi.org/10.1158/0008-5472.CAN-24-4425/). Additionally, the proliferation of tumor-related regulatory T cells in circulation was linked to treatment efficacy in triple-negative breast cancer, where increased Treg proliferation correlated with poor responses to chemoimmunotherapy (ref: Jeon doi.org/10.1158/1078-0432.CCR-24-3283/). Furthermore, tumor-derived CCL16 was found to normalize tumor vasculature and enhance immunotherapy efficacy in hepatocellular carcinoma, indicating that targeting the tumor microenvironment can improve therapeutic outcomes (ref: Chen doi.org/10.1158/0008-5472.CAN-24-4323/). These insights highlight the importance of understanding the tumor microenvironment in developing effective cancer therapies.

Genomic Alterations and Cancer Progression

Genomic alterations, particularly in circulating tumor DNA (ctDNA), are pivotal in understanding cancer progression and patient prognosis. A study on metastatic castration-resistant prostate cancer revealed that pathogenic genomic alterations in ctDNA were associated with overall survival, emphasizing the need for integrating genomic biomarkers into clinical prognostic models (ref: Halabi doi.org/10.1016/j.eururo.2025.07.011/). Additionally, innovative genome editing technologies, such as programmable chromosome engineering, have been developed to facilitate precise and efficient large-scale DNA manipulations, which could enhance our understanding of cancer genomics (ref: Sun doi.org/10.1016/j.cell.2025.07.011/). Moreover, the analysis of clone copy number diversity in lung cancer demonstrated a link between genomic diversity and survival, providing insights into the evolutionary dynamics of tumors (ref: Pawlik doi.org/10.1038/s41586-025-09398-w/). These findings collectively underscore the significance of genomic alterations in shaping cancer behavior and guiding therapeutic strategies.

Therapeutic Strategies and Drug Development

Recent advancements in therapeutic strategies and drug development are paving the way for more effective cancer treatments. The introduction of MUTE-Seq, an ultrasensitive method for detecting low-frequency mutations in cfDNA, represents a significant leap in precision oncology, allowing for the identification of mutations that could inform treatment decisions (ref: Ye doi.org/10.1002/adma.202505208/). Additionally, the role of Jab1 in regulating homologous recombination repair-related RNAs has been identified as a potential target to enhance sensitivity to PARP inhibitors in triple-negative breast cancer, suggesting new avenues for therapeutic intervention (ref: Peng doi.org/10.1186/s12943-025-02422-7/). Furthermore, the application of semaglutide in high-risk patients demonstrated its ability to promote a pro-regenerative profile in bone marrow-derived progenitor cells, indicating its potential beyond diabetes management (ref: Park doi.org/10.1093/eurheartj/). These developments highlight the ongoing efforts to refine cancer therapies and improve patient outcomes through innovative drug development and targeted strategies.

Clinical Trials and Patient Outcomes

Clinical trials continue to play a vital role in advancing cancer treatment and understanding patient outcomes. A pivotal trial evaluated the association of circulating kidney injury molecule-1 (KIM-1) with outcomes in patients receiving adjuvant immunotherapy for renal cell carcinoma, revealing its potential as a biomarker to guide treatment decisions (ref: Rini doi.org/10.1016/j.annonc.2025.08.007/). Additionally, the integration of ctDNA dynamics in monitoring treatment response in extensive-stage small cell lung cancer demonstrated its utility in informing first-line therapy decisions, potentially leading to improved patient management (ref: Ciardullo doi.org/10.1158/1078-0432.CCR-25-2011/). Furthermore, the exploration of Jab1's role in modulating RNA stability for enhancing PARP inhibitor sensitivity underscores the importance of understanding molecular mechanisms in clinical outcomes (ref: Peng doi.org/10.1186/s12943-025-02422-7/). These findings collectively emphasize the significance of clinical trials in elucidating biomarkers and therapeutic strategies that can ultimately improve patient outcomes.

Metabolic and Physiological Insights

Metabolic alterations in cancer are gaining attention as potential biomarkers and therapeutic targets. A study on acute myeloid leukemia revealed that plasma lipid levels could predict chemotherapy response and survival, suggesting that metabolic profiling may serve as a valuable tool in patient management (ref: O'Brien doi.org/10.1182/blood.2025029132/). Additionally, the investigation of Jab1's role in regulating homologous recombination repair-related RNAs highlights the interplay between metabolism and cancer therapy, particularly in enhancing sensitivity to PARP inhibitors in triple-negative breast cancer (ref: Peng doi.org/10.1186/s12943-025-02422-7/). These insights into the metabolic landscape of cancer not only provide a deeper understanding of tumor biology but also open new avenues for therapeutic interventions aimed at metabolic pathways.

Key Highlights

  • ctDNA detection after therapy is more prognostic than conventional imaging in large B-cell lymphoma, with undetectable ctDNA correlating with 96% PFS (ref: Roschewski doi.org/10.1200/JCO-25-01534/)
  • Plasma lipid levels predict chemotherapy response and survival in acute myeloid leukemia, indicating the potential of metabolic profiling (ref: O'Brien doi.org/10.1182/blood.2025029132/)
  • Clostridium butyricum enhances anti-PD-1 efficacy in colorectal cancer models, suggesting probiotics may improve immunotherapy outcomes (ref: Xie doi.org/10.1016/j.ccell.2025.07.012/)
  • Gut microbiota influences colorectal cancer liver metastasis by altering neutrophil recruitment, highlighting the role of the microbiome in cancer progression (ref: Zheng doi.org/10.1158/0008-5472.CAN-24-4425/)
  • Pathogenic genomic alterations in ctDNA predict overall survival in metastatic castration-resistant prostate cancer, emphasizing the need for genomic biomarkers in prognosis (ref: Halabi doi.org/10.1016/j.eururo.2025.07.011/)
  • MUTE-Seq allows for ultrasensitive detection of low-frequency mutations in cfDNA, enhancing precision oncology capabilities (ref: Ye doi.org/10.1002/adma.202505208/)
  • Increased proliferation of tumor-related Tregs correlates with poor treatment response in triple-negative breast cancer, indicating immune dynamics' impact on therapy (ref: Jeon doi.org/10.1158/1078-0432.CCR-24-3283/)
  • Semaglutide promotes a pro-regenerative profile in high-risk patients, suggesting its broader therapeutic potential beyond diabetes management (ref: Park doi.org/10.1093/eurheartj/)

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