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

Circulating Tumor DNA and Cancer Prognostics

The prognostic significance of circulating tumor DNA (ctDNA) has been increasingly recognized in various cancer types, particularly in advanced breast cancer. A study highlighted the importance of baseline ctDNA levels, including the mean variant allele frequency (VAF) and the number of driver somatic mutations, which were found to be significant predictors of progression-free survival (PFS) and overall survival (OS) (ref: Mamann doi.org/10.1016/j.annonc.2025.06.015/). Specifically, a ctDNA-based risk model demonstrated independent prognostic capabilities compared to traditional RECIST criteria, indicating that ctDNA dynamics during treatment could provide critical insights into patient outcomes. Another study focused on the mutational landscape of ctDNA after progression on CDK4/6 inhibitors, revealing that mutations in TP53, PIK3CA, and RB1 were associated with shorter PFS, suggesting that ctDNA profiling could guide therapeutic decisions in metastatic HR-positive/HER2-negative breast cancer (ref: Jeselsohn doi.org/10.1016/j.esmoop.2025.105506/). Furthermore, the application of cell-free RNA (cfRNA) analysis in colorectal cancer detection showcased the potential of liquid biopsies in identifying cancer-specific alterations, emphasizing the role of ctDNA and cfRNA in early cancer detection and monitoring (ref: Ju doi.org/10.1038/s41587-025-02731-8/). Lastly, advancements in cell-free DNA testing for pancreatic cancer demonstrated the feasibility of using cfDNA characteristics for early detection and prognosis, highlighting the growing relevance of liquid biopsy technologies in clinical oncology (ref: Wu doi.org/10.1038/s41467-025-61890-z/).

Liquid Biopsy Technologies and Applications

Liquid biopsy technologies have emerged as transformative tools in cancer diagnosis and monitoring, offering non-invasive alternatives to traditional tissue biopsies. A study introduced a novel liquid biopsy platform utilizing CRISPR/Cas13a and gold nanoarrays for the sensitive detection of microRNAs in extracellular vesicles, specifically targeting colorectal cancer biomarkers (ref: Chen doi.org/10.1021/acsnano.5c06940/). This platform enhances the specificity and sensitivity of liquid biopsies, paving the way for personalized medicine approaches. Additionally, the development of a personalized neoantigen vaccine demonstrated significant immune responses in melanoma patients, showcasing the potential of combining liquid biopsy insights with immunotherapy strategies (ref: Blass doi.org/10.1016/j.cell.2025.06.019/). Furthermore, the identification of elevated levels of specific cell-free RNAs in pregnancies complicated by preeclampsia underscores the versatility of liquid biopsy applications beyond oncology, indicating its potential in maternal-fetal medicine (ref: Gong doi.org/10.1038/s41467-025-61931-7/). The integration of advanced screening methods, such as droplet microfluidics for protein screening, further exemplifies the innovative approaches being developed to enhance liquid biopsy technologies (ref: Chen doi.org/10.1021/jacs.5c04962/).

Microbiome and Cancer Interactions

The interplay between the microbiome and cancer has garnered significant attention, particularly regarding its influence on cancer progression and treatment responses. A study demonstrated that modifications in microbiome-derived cell-free RNA could effectively discriminate colorectal cancer samples, highlighting the potential of microbiome analysis in cancer detection (ref: Ju doi.org/10.1038/s41587-025-02731-8/). This finding suggests that the microbiome's activity can be reflected in circulating biomarkers, providing a novel avenue for early cancer diagnosis. Additionally, research into the effects of gut microbiota on placental development revealed that microbial composition can influence angiogenesis and fetal growth, indicating broader implications for understanding cancer's environmental interactions (ref: Coskun doi.org/10.1073/pnas.2426341122/). In therapeutic contexts, the modulation of the tumor microenvironment through agents like dasatinib has shown promise in enhancing immunotherapy efficacy, suggesting that microbiome interactions may also play a role in treatment responses (ref: Redin doi.org/10.1158/0008-5472.CAN-24-2772/). These studies collectively emphasize the importance of considering microbiome dynamics in cancer research and treatment strategies.

Immunotherapy and Tumor Microenvironment

Immunotherapy continues to evolve as a cornerstone of cancer treatment, with recent studies exploring various strategies to enhance its efficacy. A multicenter phase II study evaluated the combination of nivolumab and ipilimumab in metastatic castration-resistant prostate cancer, revealing a clinical response rate of 32% overall, with higher rates observed in patients with specific genomic alterations (ref: Leone doi.org/10.1200/JCO-24-02637/). This underscores the potential for personalized immunotherapy approaches based on tumor genetics. Additionally, the combination of pembrolizumab with radiotherapy demonstrated systemic antitumor immune responses in immunologically cold non-small cell lung cancer, suggesting that radiation may sensitize tumors to immune checkpoint inhibitors (ref: Huang doi.org/10.1038/s43018-025-01018-w/). Furthermore, innovative strategies such as using an anti-CD117 antibody for conditioning in stem cell transplantation highlight the ongoing efforts to minimize toxicity while maximizing therapeutic efficacy in patients with specific genetic backgrounds (ref: Agarwal doi.org/10.1038/s41591-025-03817-1/). These findings collectively illustrate the dynamic landscape of immunotherapy and its integration with other treatment modalities to improve patient outcomes.

Cell-Free RNA and Cancer Detection

Cell-free RNA (cfRNA) analysis has emerged as a promising tool for cancer detection and monitoring, with several studies highlighting its potential applications. One study developed a model for early detection and prognosis prediction of pancreatic cancer using cfDNA characteristics, including end motif and fragmentation features, demonstrating the feasibility of liquid biopsy approaches in this challenging cancer type (ref: Wu doi.org/10.1038/s41467-025-61890-z/). Additionally, the use of nanosensor chemical cytometry to unveil aging heterogeneities in human dermal fibroblasts illustrates the versatility of cfRNA analysis beyond oncology, providing insights into regenerative medicine (ref: Song doi.org/10.1038/s41467-025-61590-8/). Moreover, the identification of high mitochondrial DNA content as a marker for acute myeloid leukemia highlights the potential of cfRNA profiling in stratifying patients based on metabolic states and therapeutic vulnerabilities (ref: Pereira-Martins doi.org/10.1038/s41392-025-02303-x/). These advancements in cfRNA technologies underscore their critical role in enhancing cancer detection and understanding tumor biology.

Extracellular Vesicles and Biomarkers

Extracellular vesicles (EVs) have gained prominence as carriers of biomarkers for various diseases, including cancer. Recent research characterized the transcriptome of circulating EVs in obese and lean individuals, identifying specific gene expressions associated with obesity that may have implications for disease susceptibility (ref: Chatterjee doi.org/10.1016/j.xgen.2025.100925/). This study emphasizes the potential of EVs in reflecting systemic metabolic states and their relevance in cancer research. Additionally, an advanced liquid biopsy platform utilizing CRISPR/Cas13a for the detection of microRNAs in EVs demonstrated high sensitivity and specificity for colorectal cancer biomarkers, showcasing the innovative approaches being developed in liquid biopsy technologies (ref: Chen doi.org/10.1021/acsnano.5c06940/). Furthermore, the exploration of mRNA degradation pathways in Ewing sarcoma highlights the functional roles of EVs in cancer biology, suggesting that targeting these pathways could represent a therapeutic vulnerability (ref: Galvan doi.org/10.1038/s41467-025-61725-x/). Collectively, these studies illustrate the expanding role of EVs in cancer diagnostics and therapeutics.

Molecular Mechanisms in Cancer Progression

Understanding the molecular mechanisms underlying cancer progression is crucial for developing effective therapies. Recent findings revealed that JAK2 inhibition in myeloproliferative neoplasms leads to clonal selection of RAS pathway mutations, indicating that targeted therapies can influence tumor evolution (ref: Maslah doi.org/10.1038/s41467-025-60884-1/). This highlights the need for continuous monitoring of genetic alterations during treatment. Additionally, a study on aging heterogeneities in human dermal fibroblasts utilized nanosensor chemical cytometry to provide insights into the regenerative potential of these cells, emphasizing the importance of cellular aging in therapeutic outcomes (ref: Song doi.org/10.1038/s41467-025-61590-8/). Moreover, the safety and efficacy of intra-arterial transplantation of autologous mesoangioblasts in mutation carriers demonstrated the potential of regenerative therapies in addressing mitochondrial diseases, which may have implications for cancer treatment as well (ref: van Tienen doi.org/10.1016/j.ymthe.2025.07.005/). These studies collectively contribute to a deeper understanding of the molecular landscape of cancer and its therapeutic implications.

Genomic Alterations and Resistance Mechanisms

Genomic alterations play a pivotal role in cancer progression and treatment resistance. Recent studies have identified various resistance mechanisms associated with targeted therapies. For instance, the analysis of circulating tumor DNA after progression on CDK4/6 inhibitors revealed mutations in key genes such as TP53 and PIK3CA, which were linked to decreased progression-free survival (ref: Jeselsohn doi.org/10.1016/j.esmoop.2025.105506/). This underscores the importance of genomic profiling in understanding resistance mechanisms. Additionally, the characterization of NUT carcinoma through broad-panel next-generation sequencing highlighted the diverse genomic landscape of this rare cancer, providing insights into potential therapeutic targets (ref: Kim doi.org/10.1158/1078-0432.CCR-25-1071/). Furthermore, the exploration of DNA damage response deficiencies in heavily pretreated patients emphasized the challenges in developing effective therapies in this context, revealing the need for innovative approaches to overcome resistance (ref: Silverman doi.org/10.1158/1078-0432.CCR-25-1248/). These findings collectively illustrate the complexity of genomic alterations in cancer and their implications for treatment strategies.

Key Highlights

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