Tumor-Educated Platelet RNA Profiling for Cancer Detection and Treatment Monitoring: A Comprehensive Narrative Review

Circulating Tumor Function: A Systems Biology Framework for Liquid Biopsy in Genitourinary Cancers

Liquid biopsy enables minimally invasive detection and longitudinal monitoring of tumor-derived material in blood and urine. In genitourinary cancers, most applications have focused on genomic alterations in circulating tumor DNA (ctDNA), together with circulating tumor cells (CTCs), extracellular vesicles (EVs), and cell-free RNAs. These measurements are clinically informative but are often interpreted as isolated, predominantly descriptive biomarkers and therefore incompletely represent the adaptive processes that determine progression and treatment response. We propose circulating tumor function (CTF) as a systems biology framework for integrating tumor-derived and host-derived genomic, regulatory, metabolic, redox, and immune signals obtained through serial liquid biopsy. CTF is not a single analyte or assay; rather, it is an inference model intended to generate interpretable functional states, including proliferative activity, immune evasion, metastatic potential, metabolic stress, and therapeutic adaptation. We review the contributions and limitations of ctDNA, ncRNA networks, EV-mediated signaling, redox biomarkers, and tumor–host crosstalk in prostate, bladder, renal, and testicular cancers. We also outline the analytical and clinical validation required to determine whether integrated CTF models provide incremental value over established single-analyte approaches. This framework may help reposition liquid biopsy from molecular detection toward functional precision oncology.

Liquid biopsy biomarkers for cancer detection, treatment monitoring, and clinical outcome prediction

Liquid biopsy now provides minimally invasive access to tumor-derived genomic and epigenetic information across the lung cancer continuum, and its clinical role continues to expand. This review examines that role across cancer detection (screening and diagnosis), treatment monitoring (advanced-disease genotyping, minimal residual disease (MRD) assessment, and resistance profiling at progression), and clinical outcome prediction. Plasma-based genotyping is now well established in advanced non-small cell lung cancer (NSCLC), while circulating tumor DNA (ctDNA)-based MRD detection in the curative-intent setting has accumulated a substantial evidence base over the past 5 years. Cell-free DNA (cfDNA) methylation, fragmentomics, and circulating tumor RNA (ctRNA) are emerging as complementary modalities, particularly when tumor shedding is low. We also consider concordance between liquid and tissue biopsies, the use of cerebrospinal fluid (CSF) ctDNA in central nervous system (CNS)-involved disease, and the practical issues of cost, reimbursement, and access that shape clinical adoption. The current state of the field can be framed across three tiers of evidence, with established applications, applications under prospective evaluation, and applications not yet ready for routine clinical use. No multi-cancer early detection (MCED) test has shown a mortality benefit to date, and ctDNA-guided treatment changes in metastatic disease still lack randomized overall-survival data.

Liquid Biopsies for Cancer: A Translational Science Review.

Importance Circulating tumor DNA (ctDNA) evaluation, in which fragments of tumor DNA circulating in a patient's bloodstream are extracted and analyzed, can be used to monitor cancer progression, detect residual cancer after treatment, and identify genetic changes within cancer cells that could affect treatment response. Observations ctDNA sequencing identifies cancer cell gene variants that inform the selection of molecularly directed therapies in several types of cancer, including non-small cell lung cancer, colorectal cancer, and breast cancer. Increases or decreases in ctDNA levels can indicate treatment response (ctDNA decrease) or cancer cell resistance and recurrence (ctDNA increase). Detecting ctDNA after curative intent therapy correlates strongly with cancer recurrence and poorer survival. In a meta-analysis of 1725 patients undergoing treatment for urothelial carcinoma, higher ctDNA levels were associated with poorer survival outcomes (hazard ratio for disease-free survival, 20.69 [95% CI, 9.63-44.43]; P < .001). This association was also observed in adjuvant settings (hazard ratio for disease-free survival, 4.51 [95% CI, 3.04-6.69]; P < .001) and in patients undergoing systemic therapy for metastatic disease (hazard ratio for overall survival, 2.0 [95% CI, 1.25-3.38]; P = .004; absolute rates not available). ctDNA detection may indicate minimal residual disease, defined as cancer cells detectable only by highly sensitive testing (eg, detection of 1 cancer cell in a population of 1 million normal cells) before disease progression is identified with imaging. Detecting an early increase in ctDNA and/or a novel sequence variation that may confer resistance to standard treatment can guide therapeutic decisions, such as changing to a new treatment, before tumor progression is detectable with conventional imaging. In a prospective cohort study of 130 patients with colorectal cancer, molecular relapse of disease was detected approximately 8.7 months earlier compared with standard-of-care imaging surveillance (5.5 months vs 14.2 months; P < .001). Similarly, patients with undetectable ctDNA levels may be able to discontinue therapy and be monitored, preventing potentially unnecessary exposure to chemotherapy that may have substantial adverse effects. However, the optimal timing of ctDNA testing, management of positive results in the absence of radiographic disease, and the cost-effectiveness of serial monitoring remain unclear. Conclusions and Relevance ctDNA, consisting of small DNA fragments from cancer cells that can be analyzed in human blood, can help clinicians monitor cancer progression, detect minimal residual cancer, and identify genetic variants that may help guide treatment decisions. Use of ctDNA may help select best treatment and timing of therapy for a patient with cancer, but optimal clinical applications remain unclear.

Single-Cell RNA Sequencing of Pancreatic Circulating Tumor Cells.

Circulating tumor DNA in early breast cancer: Evidence, challenges, next steps

Circulating tumor DNA (ctDNA) is a tumor‐derived, circulating bioanalyte that can be detected in blood using minimally invasive, blood‐based biomarker procedures and has prognostic value in early breast cancer. Quantitative features of ctDNA, including baseline detectability and levels, have shown prognostic potential in early breast cancer by reflecting tumor burden and biologic aggressiveness, thereby supporting risk stratification. Post‐treatment ctDNA detection may identify minimal residual disease and can precede radiologic or symptomatic recurrence by several months to years. Nevertheless, ctDNA has not yet been adopted in routine clinical practice in early breast cancer, partly because of biologic constraints, including low and heterogeneous tumor DNA shedding, as well as pre‐analytical and analytical variability that can affect testing sensitivity. Ongoing efforts are focused on methodological standardization and clarification of the clinically actionable context. This narrative review examines the challenges in applying ctDNA to early breast cancer, spanning patient selection, sampling logistics, specimen handling, assay performance, and sources of assay failure. The authors outline determinants of ctDNA measurement that restrict the proportion of evaluable patients and limit translation to clinical practice and then summarize evidence supporting ctDNA for early response monitoring during neoadjuvant therapy, postoperative minimal residual disease detection, and longitudinal molecular surveillance. Finally, ctDNA‐guided therapeutic interception strategies and emerging multimodal cell‐free DNA approaches are discussed.

Circular RNAs in Plasma and Beyond: Potential Biomarkers for Breast Cancer

: Breast cancer (BC) continues to be a major cause of cancer-related mortality among women, and early diagnosis remains critical for improving survival outcomes. Conventional tissue biopsy and imaging techniques are constrained by invasiveness and limited sensitivity in early-stage disease, whereas routine serum tumor markers lack sufficient specificity for reliable early detection. Circular RNAs (circRNAs) have increasingly been recognized as promising non-invasive biomarkers, owing to their remarkable stability and detectability in plasma. Here, we summarize the current landscape of plasma circRNAs as diagnostic, prognostic, and chemoresistance-related biomarkers in BC, emphasizing their clinical relevance in therapy selection, subtype stratification, treatment monitoring, and recurrence prediction. Aberrant circRNA expression in the plasma of BC patients has been associated with tumor size, stage, and molecular subtype, and functionally linked to cell survival, metastasis, and drug resistance. Importantly, circRNAs may complement conventional approaches including imaging and serum markers, and their integration with other circulating analytes could enhance diagnostic precision and support individualized therapeutic decisions. Our work consolidates recent advances in circRNA research across preoperative, postoperative, drug resistance, and recurrence settings, providing a framework for non-invasive diagnosis, clinical decision-making, and outcome prediction in BC management. This review aims to bridge tissue-based discoveries and plasma-based applications for the clinical translation of circRNAs.