Search Results (2,401)

The adoption of liquid biopsy approaches in clinical practice has triggered a significant paradigm shift in the diagnostic, prognostic, and predictive outcomes for cancer patients. Circulating tumor DNA (ctDNA) is considered a valuable biomarker for monitoring tumor burden and its mutational dynamics. In this context, not all cell-free DNA (cfDNA) molecules are derived from tumor cells. Furthermore, due to tumor heterogeneity, not all ctDNA molecules contain cancer-associated alleles, complicating the direct quantification of the circulating tumor allele fraction (cTF) within the total cfDNA. Cancer arises from the accumulation of multiple genetic and epigenetic changes. Each of these molecular features can be exploited as the basis of methodological strategies used in ctDNA quantification. Different layers of omics data, from genomics, evaluating mutational analysis of somatic single-nucleotide variants and copy number alterations, to epigenomics, primarily consisting of the evaluation of methylation profiles and fragmentation patterns, can be used for this purpose. Some of these approaches can be effective in a multi-modal manner. To date, the quantification approaches for estimating cTF vary enormously, making direct comparisons and an assessment of their translational value challenging. Moreover, the lack of regulatory approval for many of these assays is a critical barrier to their widespread clinical adoption. This review explores the different omics approaches described for ctDNA quantification, outlining strengths and limitations, and highlighting their valuable applications in clinical settings. Full article

Background/Objectives: Appropriate biomarkers are necessary for early diagnosis and multidisciplinary treatment of pancreatic ductal adenocarcinoma (PDAC). In recent years, the clinical utility of circulating tumor cells (CTC) as biomarkers for various can-cers has been reported; however, their detection rate in PDAC remains low, and clinical evidence is not yet established. CTC detection methods with high reliability and per-formance are essential for clarifying the importance of CTC in patients with PDAC. Methods: A total of 5 mL peripheral blood samples were collected from 38 patients newly diagnosed with PDAC and 17 healthy controls. Negatively enriched cells were immunofluorescently stained with EpCAM-phycoerythrin and cell surface vi-mentin-fluorescein isothiocyanate (CSV). Images were automatically captured using an all-in-one fluorescence microscope. Cellular regions were detected from these images, and the average luminance of the cellular regions was calculated. A total of 9086 and 1071 cell images were obtained from patients with PDAC and healthy controls, respec-tively. Results: In the EpCAM assay, a threshold that included 95% of healthy individuals was optimal for distinguishing patients with PDAC from healthy controls, with a sensi-tivity, specificity, and area under the curve of 0.74, 0.76, and 0.84, respectively. At this threshold, the CTC-positivity rate in patients with PDAC was 76.3%. Conversely, the CSV assay failed to demonstrate a valid threshold to distinguish patients with PDAC from healthy controls. No significant differences were found between CTC and clini-copathological features among patients with PDAC. Conclusions: The method using high-resolution image scanning has the potential to identify CTC with greater objectiv-ity by quantifying cell luminance values. Full article

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality globally, driven by marked molecular and cellular heterogeneity that complicates diagnosis and treatment. Despite advances in targeted therapies and immunotherapies, treatment resistance frequently emerges, and clinical benefits remain limited to specific molecular subtypes. To improve early detection and dynamic monitoring, novel diagnostic strategies—including liquid biopsy, low-dose computed tomography scans (CT) with radiomic analysis, and AI-integrated multi-modal platforms—are under active investigation. Non-invasive sampling of exhaled breath, saliva, and sputum, and high-throughput profiling of peripheral T-cell receptors and immune signatures offer promising, patient-friendly biomarker sources. In parallel, multi-omic technologies such as single-cell sequencing, spatial transcriptomics, and proteomics are providing granular insights into tumor evolution and immune interactions. The integration of these data with real-world clinical evidence and machine learning is refining predictive models and enabling more adaptive treatment strategies. Emerging therapeutic modalities—including antibody–drug conjugates, bispecific antibodies, and cancer vaccines—further expand the therapeutic landscape. This review synthesizes recent advances in NSCLC diagnostics and treatment, outlines key challenges, and highlights future directions to improve long-term outcomes. These advancements collectively improve personalized and effective management of NSCLC, offering hope for better-quality survival. Continued research and integration of cutting-edge technologies will be crucial to overcoming current challenges and achieving long-term clinical success. Full article

Background: Glioblastoma (GBM) remains refractory to chemoradiotherapy. Glial populations—microglia/monocyte-derived macrophages, reactive astrocytes, and the oligodendrocyte lineage—shape both treatment resistance and radiation-related brain injury. Scope: We synthesize how myeloid ontogeny and plasticity, astrocytic hubs (IL-6/STAT3, TGF-β, connexin-43/gap junctions), and oligodendrocyte precursor cells (OPCs)–linked programs intersect with DNA-damage responses, hypoxia-driven metabolism, and extracellular vesicle signaling to support tumor fitness while predisposing normal brain to radiotoxicity. Translational implications: Convergent, targetable pathways (IL-6/JAK–STAT3, TGF-β, chemokine trafficking, DDR/senescence) enable co-design of radiosensitization and neuroprotection. Pragmatic levers include myeloid reprogramming (CSF-1R, CCR2), astrocyte-axis modulation (STAT3, TGF-β, Cx43), and brain-penetrant DDR inhibition (e.g., ATM inhibitors), paired with delivery strategies that raise intratumoral exposure while sparing healthy tissue (focused-ultrasound blood–brain barrier opening, myeloid-targeted dendrimers; Tumor Treating Fields as an approved adjunct therapy). Biomarker frameworks (TSPO-PET, macrophage-oriented MRI radiomics, extracellular vesicle liquid biopsy) can support selection and pharmacodynamic readouts alongside neurocognitive endpoints. Outlook: Timing-aware combinations around radiotherapy and hippocampal/white-matter sparing offer a near-term roadmap for “glia-informed” precision radiotherapy. Full article

Background/Objectives: Cervical cancer is one of the most frequent malignancies among women in Kazakhstan, where human papillomavirus (HPV) vaccination was initiated in 2024. Despite the implementation of vaccination and cytology-based screening programs, diagnostic limitations remain, and local evidence linking HPV infection to clinical outcomes is scarce. This study aimed to evaluate the correlation between HPV status, cervical cytology results, colposcopic impression, and biopsy results in a non-vaccinated female population. Methods: A cross-sectional study was conducted at the University Medical Center, Astana, between November 2024 and March 2025. A total of 396 women of reproductive age were enrolled. Cervical samples underwent liquid-based cytology and high-risk HPV testing with the RealBest assay. Colposcopy was performed following abnormal cervical cytology results, and colposcopy-guided biopsies were obtained where indicated. Sociodemographic characteristics were assessed, and associations between HPV genotype and clinical outcomes were analyzed using descriptive and inferential statistics. Results: HPV infection was detected in 140 women (35.4%). HPV-16 was the most common genotype (11.4%), followed by HPV-52 (6.6%) and HPV-33 (5.3%). Among 198 women evaluated by colposcopy, abnormal findings were observed in 72.2%, with HPV-16 showing a significant association with higher-grade abnormalities (p < 0.001). Biopsies were available for 40 participants: 12 had CIN I, 12 had CIN II, 10 had CIN III, and 4 had carcinoma in situ. HPV-16 was the only genotype significantly linked to CIN II/III lesions. Conclusions: HPV-16 was strongly associated with abnormal colposcopic findings and high-grade histology, underscoring its oncogenic importance. The prevalence of HPV-52 and HPV-33 further supports the need for HPV nonavalent vaccination. These findings highlight the importance of HPV-based screening, genotype-specific triage, and expanded vaccination to reduce cervical cancer incidence in Kazakhstan. Full article

Background/Objectives: Conventional imaging assesses therapy response in stage IV solid-tumor patients in 8- to 12-week intervals, delaying detection of non-responders. We evaluated a quantitative PCR (qPCR) assay that interrogates size-distributed cell-free DNA (cfDNA) fragments to provide earlier insights into treatment efficacy. Methods: In this prospective study, 128 patients with metastatic lung, breast, or colorectal cancer provided plasma 12–21 days after the first dose of a new systemic regimen. The qPCR targets multi-copy retrotransposon element fragments of greater than 80 bp, greater than 105 bp, and greater than 265 bp, as well as an internal control. A model integrates these quantities into a Progression Score (PS) ranging from 0 to 100; higher values indicate probable disease progression. Results: The PS model yielded an area under (AUC) the receiver-operating-characteristic (ROC) curve of 0.93 for predicting radiographic progression at first imaging. Scores were strongly bimodal: 92% of patients with PS > 90 progressed, whereas 95% with PS < 10 did not. Intermediate scores (10–90) comprised a mixed cohort. Assay performance was unaffected by tumor genomic profile. Conclusions: This cfDNA-based Progression Score (PS) assay enables tumor- and therapy-agnostic, non-invasive monitoring of treatment response as early as two weeks after initiation. By flagging ineffective regimens well before standard imaging, the test can accelerate clinical decision-making, reduce exposure to futile therapy, and potentially improve outcomes in stage IV cancer. Early treatment plan changes may also avoid the high costs of ineffective treatments, prevent downstream toxicity-related hospitalizations, and free up limited imaging and infusion-suite capacity—yielding savings for patients, payers, and healthcare systems. Full article

Cancer and aging are two distinct biological processes with shared cellular pathways, such as cellular senescence, DNA damage repair, and metabolic reprogramming. However, the outcomes of these processes differ in terms of proliferation. Understanding biomarkers related to aging and cancer opens a pathway for therapeutic interventions and more effective prevention, detection, and treatment strategies. Biomarkers, ranging from molecular to phenotypic indicators, play an important role in early detection, risk assessment, and prognosis in this endeavor. This review comprehensively examines key biomarkers associated with cancer and aging, highlighting their importance in early diagnostic strategies. The review discusses recent advances in biomarker-based diagnostic technologies, such as liquid biopsy, multi-omics integration, and artificial intelligence, and emphasizes their novel potential for early detection, accurate risk assessment, and personalized therapeutic interventions in cancer and aging science. We also explore the current state of biosensor development and clinical application cases. Finally, we discuss the limitations of current early diagnostic methods and propose future research directions to enhance biomarker-based diagnostic technologies. Full article

Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer death worldwide. Early detection of lung cancer can lead to identification of the cancer at its initial treatable stages and improves survival. Low-dose CT scan (LDCT) is currently the gold standard for lung cancer screening in high-risk individuals. Despite the observed stage migration and consistently demonstrated disease-specific overall survival benefit, LDCT has inherent limitations, including false-positive results, radiation exposure, and low compliance. Recently, new techniques have been investigated for early detection of lung cancer. Several studies have shown that liquid biopsy biomarkers such as circulating cell-free DNA (cfDNA), microRNA molecules (miRNA), circulating tumor cells (CTCs), tumor-derived exosomes (TDEs), and tumor-educated platelets (TEPs), as well as volatile organic compounds (VOCs), have the power to distinguish lung cancer patients from healthy subjects, offering potential for minimally invasive and non-invasive means of early cancer detection. Furthermore, recent studies have shown that the integration of artificial intelligence (AI) with clinical, imaging, and laboratory data has provided significant advancements and can offer potential solutions to some challenges related to early detection of lung cancer. Adopting AI-based multimodality strategies, such as multi-omics liquid biopsy and/or VOCs’ detection, with LDCT augmented by advanced AI, could revolutionize early lung cancer screening by improving accuracy, efficiency, and personalization, especially when combined with patient clinical data. However, challenges remain in validating, standardizing, and integrating these approaches into clinical practice. In this review, we described these innovative milestones and methods, as well as their advantages and limitations in screening and early diagnosis of lung cancer. Full article

Esophageal cancer (EC) continues to pose a major global health burden, ranking as the ninth most common malignancy and sixth leading cause of cancer mortality, with over 600,000 new cases and 500,000 deaths annually as of 2025. While esophagectomy has long been the standard for curative intent in resectable disease, organ preservation strategies have advanced significantly, offering viable alternatives for patients with locally advanced esophageal squamous cell carcinoma (ESCC) or those unsuitable for surgery due to comorbidities. These approaches encompass definitive chemoradiotherapy (dCRT), neoadjuvant chemoradiotherapy (nCRT) followed by active surveillance (“watch-and-wait”), and innovative integrations of immunotherapy and targeted therapies. This narrative review synthesizes evidence from recent clinical trials, systematic reviews, and international guidelines up to 2025, demonstrating that organ-sparing protocols can achieve comparable overall survival (OS) rates—often exceeding 50% at 5 years in selected cohorts-while substantially enhancing quality of life (QoL) by preserving esophageal function. For instance, the SANO trial (2025) confirmed non-inferiority of active surveillance post-nCRT, with 2-year OS of 74% versus 71% for standard surgery. Key challenges include imprecise response assessment, locoregional recurrences (20–30%), and treatment-related toxicities such as esophageal strictures. Emerging trials like ESOSTRATE and PALACE3 are evaluating immunotherapy-enhanced regimens, potentially expanding organ preservation to esophageal adenocarcinoma (EAC). With genomic biomarkers and novel modalities like proton therapy, personalized organ preservation promises to broaden applicability, reduce morbidity, and improve outcomes across histological subtypes. Additionally, recent studies emphasize the role of liquid biopsies, such as circulating tumor DNA (ctDNA), in monitoring treatment response and guiding surveillance, potentially reducing the need for invasive procedures and improving detection of minimal residual disease. The aim of this review is not only to summarize recent trials but to synthesize them into an operational framework that clinicians and researchers can apply: a decision algorithm for selecting organ preservation candidates. This is the novel element that distinguishes this work from prior narrative reviews. Full article

Gastroesophageal cancers including esophageal and gastric cancer remain major causes of global cancer mortality, primarily due to late diagnosis and high recurrence rates after curative treatment. Current surveillance methods, such as endoscopy and imaging, are invasive, costly, and often inadequate for detection. Blood-based biomarkers (“liquid biopsies”) offer a minimally invasive alternative capable of real-time tumor monitoring. In this review, we summarize recent advances across all major classes of blood-derived biomarkers: circulating tumor DNA (ctDNA), methylated DNA, cell-free RNAs (microRNAs, lncRNAs, circRNAs), circulating proteins, autoantibodies, circulating tumor cells, extracellular vesicles, and metabolites. Reviewing the existing literature on gastroesophageal cancers, we highlight current evidence, validation phases, performance metrics, and limitations. Special attention is given to clinical trial evidence, including ctDNA monitoring studies, that demonstrated earlier recurrence detection compared to imaging. While blood-based biomarker analysis has not yet supplanted endoscopy as standard of care in gastroesophageal cancer surveillance, the convergence of multi-analyte assays, AI, and clinical validation trials positions liquid biopsy as a transformative tool in the surveillance of gastroesophageal cancers. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, with patient outcomes highly dependent on early and accurate diagnosis. However, existing diagnostic methods, such as colonoscopy, fecal occult blood testing, and imaging, are often invasive, costly, or lack sufficient sensitivity and specificity, particularly in early-stage disease. In this context, aptamers, which are synthetic single-stranded oligonucleotides capable of binding to specific targets with high affinity, have emerged as a powerful alternative to antibodies for biosensing applications. This review provides a comprehensive overview of aptamer-based strategies for CRC detection, spanning from biomarker discovery to clinical translation. We first examine established and emerging CRC biomarkers, including those approved by regulatory agencies, described in patents, and shared across multiple cancer types. We then discuss recent advances in aptamer selection and design, with a focus on SELEX variants and in silico optimization approaches tailored to CRC-relevant targets. The integration of aptamers into cutting-edge sensing platforms, such as electrochemical, optical, and nanomaterial-enhanced aptasensors, is highlighted, with emphasis on recent innovations that enhance sensitivity, portability, and multiplexing capabilities. Furthermore, we explore the convergence of aptasensing with microfluidics, and wearable technologies to enable intelligent, miniaturized diagnostic systems. Finally, we consider the clinical and regulatory pathways for point-of-care implementation, as well as current challenges and opportunities for advancing the field. By outlining the technological and translational trajectory of aptamer-based CRC diagnostics, this review aims to provide a roadmap for future research and interdisciplinary collaboration in precision oncology. Full article

Stereotactic ablative radiotherapy (SABR) has revolutionized the management of patients with oligometastatic and selected primary cancers due to its ability to deliver highly conformal, high-dose radiation in few fractions with minimal toxicity. However, the biological heterogeneity among patients treated with SABR results in variable outcomes, emphasizing the need for predictive and prognostic biomarkers to guide patient selection and post-treatment management. This narrative review discusses the current landscape of biomarker development in the context of SABR across tumor types. Key classes include circulating tumor DNA (ctDNA), extracellular vesicles (EVs), radiomic features, and immunological markers. We highlight the role of each biomarker category in refining therapeutic approaches, their integration into ongoing clinical trials, and future directions for personalized SABR paradigms. Translating these promising biomarker strategies into clinical SABR workflows will require further standardisation, validation, and regulatory alignment. Full article

Solid tumors collectively drive the global cancer burden, with profound molecular heterogeneity demanding precision and molecularly informed management. Advances in sequencing technologies have established molecular taxonomy as a cornerstone of clinical oncology, progressively superseding traditional histopathological classifications. Sanger sequencing remains the gold standard for validating guideline mandated actionable variants. Next-generation sequencing (NGS) has revolutionized early cancer detection through liquid biopsy applications and enabled the reclassification of diagnostically challenging tumor subtypes. Emerging long-read platforms offer unique capabilities to resolve complex genomic rearrangements, structural variants, and therapy-induced epigenetic remodeling. Consequently, therapeutic strategies are shifting from organ-centric approaches to mutation-specific interventions, exemplified by non-small-cell lung cancer, where molecular stratification drives substantial improvements in treatment response. Nevertheless, temporal tumor heterogeneity, biological contamination, and computational limitations highlight the urgent need for robust, integrated verification systems. Collectively, this evolution positions sequencing as the operational backbone of adaptive precision oncology across solid tumors. Here, we synthesize our laboratory findings with the current literature to comprehensively review the diagnostic, therapeutic, and prognostic applications of first- through fourth-generation sequencing technologies and discuss future directions in this rapidly evolving field. Full article

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide. While target therapies have changed the outcomes of patients harboring actionable mutations, resistance inevitably emerges. Circulating tumor DNA (ctDNA) offers a minimally invasive tool for capturing tumor evolution in real time. This approach enables the rapid detection of resistance mechanisms, complements or substitutes for tissue re-biopsy, and reduces the burden of invasive procedures for patients. In this review, we summarize the current evidence on the use of liquid biopsy to uncover resistance mechanisms in patients progressing on targeted therapies, with a focus on its role in dynamic tumor profiling and longitudinal disease monitoring. Full article

Cervical cancer remains a significant public health priority, particularly in low- and middle-income countries. In this context, liquid biopsy has emerged as a minimally invasive method for detecting and monitoring molecular biomarkers, offering advantages over traditional screening approaches. This systematic review included 21 studies published between 2015 and 2025 and was conducted in accordance with the PRISMA 2020 statement. The analysis examined the role of serum cytokines, circulating microRNAs (miRNAs), and circulating cell-free HPV DNA (cfHPV-DNA) in patients with cervical cancer or high-grade intraepithelial lesions. Circulating miRNAs—particularly miR-21, miR-29a, and miR-34a—are consistently associated with recurrence, tumor progression, and reduced survival. However, their immediate clinical translation remains limited by methodological variability and the lack of universal normalizers. In contrast, cfHPV-DNA, especially with ddPCR, exhibited the best study-level performance, with a specificity of 100% and a sensitivity of approximately 80–88%, across heterogeneous endpoints and analytic conditions. Consequently, cfHPV-DNA represents a promising tool for post-treatment surveillance and early detection of recurrence. Serum cytokines, such as TNF-α, IL-6, and IL-10, reflect inflammation and the tumor microenvironment. Nevertheless, their lack of standardization and variability across detection platforms restricts their reproducibility, positioning them as complementary rather than stand-alone markers. In conclusion, the evidence supports liquid biopsy as a promising tool in cervical cancer management; nonetheless, only cfHPV-DNA is currently ready for clinical application, whereas miRNAs and cytokines require multicenter validation and technical standardization before implementation. Full article