Jul 2026· International Journal of Oncology· Vol 69, pp. 1-23· 0 citations· 222 references
Medicine
TL;DR
The present review examines the emerging role of germline human leukocyte antigen class I genotype as a prognostic and predictive biomarker, explicitly integrating it with tissue-based immune contexture and liquid biopsy readouts by proposing immunoediting as a unifying mechanistic framework that links allele-specific antigen presentation to immune infiltration.
Abstract
Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men despite advances in screening and localized treatment. The clinical heterogeneity of PCa, ranging from indolent disease to aggressive, lethal phenotypes, underscores the urgent need for reliable biomarkers that improve diagnosis, prognostication and therapeutic decision-making. While prostate-specific antigen testing has reduced mortality, its limited specificity has resulted in overdiagnosis and overtreatment. The present review provides a comprehensive overview of contemporary and emerging biomarkers that support a precision-medicine approach to PCa management. The present review summarizes established and novel diagnostic, prognostic and predictive biomarkers, including serum- and urine-based assays, genomic and transcriptomic signatures and multiparametric imaging. Particular emphasis is placed on liquid biopsy technologies (circulating tumor cells, circulating tumor DNA and extracellular vesicles), which offer minimally invasive, real-time insights into tumor burden, molecular evolution and treatment resistance, although their clinical implementation remains context-dependent and is currently most established in advanced disease settings rather than routine early-stage management. The present review discusses the strengths and limitations of these platforms, highlighting disease-stage dependency, technical variability and sensitivity constraints. Beyond tumor-intrinsic markers, tissue-based immune biomarkers that capture the tumor immune microenvironment, including immune cell density, spatial organization, checkpoint expression and immune-related gene signatures, are explored. Evidence indicates that 'immune-hot' tumors characterized by CD8+ T-cell infiltration and interferon-γ signaling are associated with improved outcomes, whereas immunosuppressive macrophage- or regulatory T-cell-dominant profiles predict poor prognosis. However, these associations are not uniform across studies and PCa remains largely resistant to immunotherapy, underscoring the need to improve the understanding of immune evasion mechanisms and the contextual limitations of immune biomarkers. Furthermore, the present review examines the emerging role of germline human leukocyte antigen class I genotype as a prognostic and predictive biomarker, explicitly integrating it with tissue-based immune contexture and liquid biopsy readouts by proposing immunoediting as a unifying mechanistic framework that links allele-specific antigen presentation to immune infiltration. Finally, the present review highlights the prognostic significance of preexisting tumor-antigen-specific CD8+ T cells, which reflect an active antitumor immune response and predict a favorable progression-free survival and responsiveness to immunotherapeutic strategies. Collectively, the present review underscores the need for standardized, multimodal biomarker integration and prospective validation to enable personalized, immune-aware management of PCa.
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.
Akshee Batra, Xena Zheng, Dan Morgenstern-Kaplan et al.· Frontiers in Cell and Develo...· 0 citations
Summary Liquid biopsy, analyzing circulating tumor-derived components, including ctDNA, circulating tumor cells, microRNAs, and exosomes, has emerged as a key tool in precision oncology. This review synthesizes evidence from the past five years, covering biological mechanisms, analytical platforms, clinical applications, and implementation barriers. Evidence from multiple clinical studies suggests ctDNA shows higher sensitivity for metastatic disease monitoring than conventional biomarkers such as CA15-3 and circulating tumor cells. For minimal residual disease detection, tumor-informed assays demonstrate sensitivity of 88%–100% and provide a median lead time of 8–15 months before clinical relapse. Despite these advances, early-stage cancer detection remains suboptimal, cost-effectiveness evidence is limited, and disparities in access are increasing. We critically evaluate current technologies and translational gaps and highlight the need for standardized clinical integration pathways. Overall, liquid biopsy is transitioning from a complementary diagnostic tool toward a longitudinal framework for cancer management, although substantial methodological and systemic challenges remain.
Yan Li, Yi Wang, Rong Wang et al.· iScience· 0 citations
Liquid biopsy has rapidly emerged as one of the most promising innovations in precision oncology by providing minimally invasive access to tumor-derived biomarkers throughout the clinical course of cancer. This review analyzes the current evidence regarding the clinical applications of liquid biopsy beyond early cancer detection, emphasizing its role in molecular profiling, therapeutic selection, treatment monitoring, minimal residual disease assessment, identification of resistance mechanisms, and evaluation of tumor heterogeneity in patients with solid tumors. A comprehensive literature review was conducted using major biomedical databases, selecting high-quality publications focused on circulating tumor DNA, circulating tumor cells, extracellular vesicles, circulating RNA, and other emerging biomarkers. The available evidence demonstrates that circulating tumor DNA currently represents the most clinically validated biomarker because of its high analytical performance and increasing incorporation into precision oncology protocols. Liquid biopsy has shown particular utility in lung, colorectal, breast, and prostate cancers, where molecular information directly contributes to personalized treatment decisions. Nevertheless, several barriers continue to limit universal implementation, including high costs, limited molecular infrastructure, methodological variability, and unequal access to advanced genomic technologies, particularly in developing countries. Ongoing technological improvements, international collaboration, and methodological standardization are expected to further expand the clinical applications of liquid biopsy and facilitate its incorporation into routine oncology practice. Overall, liquid biopsy represents a transformative strategy that complements conventional tissue biopsy and supports more personalized, dynamic, and evidence-based management of solid tumors.
Ricardo Fernando, Rincón Veloz, A. Milena et al.· International science journa...· 0 citations
Breast cancer remains one of the leading causes of cancer-related mortality worldwide, and despite considerable advances in therapeutic strategies, the absence of reliable, minimally invasive diagnostic tools continues to limit early detection and real-time disease monitoring. Liquid biopsy has emerged as a transformative paradigm in oncology, offering the capacity to integrate tumor biology through the analysis of tumor-derived materials that circulate in peripheral blood and other biofluids. This review provides a comprehensive overview of the key analytes employed in liquid biopsy, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), extracellular vesicles (EVs), and protein biomarkers with particular emphasis on their translational relevance in breast cancer. Drawing on landmark clinical trials and foundational molecular studies, we highlight how these biomarkers capture spatial and temporal tumor heterogeneity in ways that conventional tissue biopsy cannot. Finally, we address the technical, clinical, and ethical challenges that still impede widespread adoption of liquid biopsy, and we outline a forward-looking research agenda oriented toward multi-omics integration and point-of-care diagnostics. Taken together, this review underscores the potential of liquid biopsy to complement existing diagnostic standards and improve how we screen for, monitor, and treat breast cancer across disease stages.
Pritam Saha Podder, Debasree Bhadra, Canio Martinelli et al.· Exploration of Targeted Anti...· 0 citations
Ovarian cancer (OC) remains a lethal gynecological malignancy with challenges in early diagnosis, treatment monitoring, and overcoming drug resistance. Liquid biopsy, a noninvasive approach analyzing tumor‐derived components in bodily fluids, has emerged as a promising tool in OC management. This review summarizes advances in liquid biopsy technologies, focusing on circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs). ctDNA enables minimally invasive assessment for diagnosis, prognosis, treatment guidance (e.g., BRCA1/2‐targeted therapy), minimal residual disease (MRD) detection, and monitoring of tumor evolution. CTCs, particularly clusters, provide insights into metastasis and therapeutic response. Emerging modalities such as tumor‐educated platelets (TEPs), circular RNAs (circRNAs), and exosomes and protease activity‐based liquid biopsy also show diagnostic and prognostic potential. Despite technical challenges like standardization and sensitivity, liquid biopsy holds significant promise for personalized OC care, with ongoing efforts to translate these technologies into clinical practice.
Jingxia Zhang, Weiyan Shan, Jie Yu et al.· Cancer Medicine· 0 citations
Prostate cancer is the second-highest cause of cancer-related incidence and the fifth-highest cause of cancer mortality in males. Prostate cancer is a heterogeneous disease with a wide spectrum of clinical behaviour, ranging from indolent to highly aggressive. Molecular approaches, such as genomic testing, can augment existing clinical risk stratifications and tailor management to the individual. Genomic tests that sample biopsy or surgical tissue can provide a molecular risk assessment and identify actionable therapy targets. Liquid biopsy, while still emerging, may provide a non-invasive alternative to tissue tests and enable longitudinal monitoring of tumour status. We first discuss the molecular landscape of prostate cancer, before providing a detailed overview of the molecular approaches available for early detection and prognostication. Furthermore, methodological considerations and barriers towards clinical implementation for these tests are discussed, highlighting areas of future research.
A. Yee, Jim Smith, Rajiv Kumar et al.· Cancer Metastasis Review· 0 citations