Search Results (470)

Oral squamous cell carcinoma (OSCC) remains one of the most common malignancies in the head and neck region, often preceded by a spectrum of oral potentially malignant disorders (OPMDs). Despite advances in diagnostic methods, reliable and non-invasive biomarkers for early detection and prognostic stratification are still lacking. In recent years, circulating cell-free DNA (cfDNA) has emerged as a promising liquid biopsy tool in several solid tumors, offering insights into tumor burden, heterogeneity, and molecular dynamics. However, its application in oral oncology remains underexplored. This study aims to review and discuss the current evidence on cfDNA quantification and mutation analysis (including TP53, NOTCH1, and EGFR) in patients with OPMDs and OSCC. Particular attention is given to cfDNA fragmentation patterns, methylation signatures, and tumor-specific mutations as prognostic and predictive biomarkers. Moreover, we highlight the challenges in standardizing pre-analytical and analytical workflows in oral cancer patients and explore the potential role of cfDNA in monitoring oral carcinogenesis. Understanding cfDNA dynamics in the oral cavity might offer a novel, minimally invasive strategy to improve early diagnosis, risk assessment, and treatment decision-making in oral oncology. Full article

The advent of personalized medicine and novel therapeutic strategies has transformed the treatment landscape of non-small cell lung cancer (NSCLC), significantly improving patient survival. However, only a minority of patients experience a durable benefit, as intrinsic or acquired resistance remains a major challenge. Understanding the complex mechanisms of resistance—linked to tumor biology, the tumor microenvironment (TME), and host factors—is crucial to overcoming these barriers. Recent innovations in diagnostics, including artificial intelligence and liquid biopsy, offer promising tools to refine therapeutic decisions. Machine Learning and Deep Learning provide predictive algorithms that enhance diagnostic accuracy and prognostic assessment. Techniques like single-cell RNA sequencing and pathomics offer deeper insights into the role of the TME. Liquid biopsy, as a minimally invasive method, enables real-time detection of circulating tumor components, facilitating the identification of predictive and prognostic biomarkers and illuminating tumor heterogeneity. These translational research advances are revolutionizing the understanding of cancer biology and are key to optimizing personalized treatment strategies. This review highlights emerging tools aimed at improving diagnostic and therapeutic precision in NSCLC, underscoring their role in decoding the interplay between tumor cells, the TME, and the host to ultimately improve patient outcomes. Full article

The global prevalence of hepatocellular carcinoma (HCC) is getting worse, leading to an urgent need for improved diagnostic and prognostic strategies. Liquid biopsy, which analyzes circulating tumor cells (CTCs), cell-free DNA (cfDNA), cell-free RNA (cfRNA), and extracellular vesicles (EVs), has emerged as a minimally invasive and promising alternative to traditional tissue biopsy. These biomarkers can be detected using sensitive molecular techniques such as digital PCR, quantitative PCR, methylation-specific assays, immunoaffinity-based CTC isolation, nanoparticle tracking analysis, ELISA, next-generation sequencing, whole-genome sequencing, and whole-exome sequencing. Despite several advantages, liquid biopsy still has challenges like sensitivity, cost-effectiveness, and clinical accessibility. Reports highlight the significance of multi-analyte liquid biopsy panels in enhancing diagnostic sensitivity and specificity. This approach offers a more comprehensive molecular profile of HCC, early detection, and tracking therapeutic treatment, particularly in those cases where single-analyte assays and imaging fail. The technological advancement in the isolation and analysis of CTC, cell-free nucleic acids, and EVs is increasing our understanding of extracting genetic information from HCC tumors and discovering mechanisms of therapeutic resistance. Furthermore, crucial information on tumor-specific transcriptomic and genomic changes can be obtained using cfRNA and cfDNA released into the peripheral blood by tumor cells. This review provides an overview of current liquid biopsy strategies in HCC and their use for early detection, prognosis, and monitoring the effectiveness of HCC therapy. Full article

Positron emission tomography (PET) imaging targeting glypican-3 (GPC3) holds promise for improving the detection and characterization of hepatocellular carcinoma (HCC). Preclinical and early clinical studies have largely utilized high-molecular-weight antibodies radiolabeled with isotopes such as ⁸⁹Zr and ¹²⁴I, demonstrating high affinity and tumor uptake but suffering from prolonged circulation times and suboptimal signal-to-background ratios. To address these limitations, interest has shifted toward low-molecular-weight vectors—synthetic peptides and small antibody fragments—labeled with shorter-lived radionuclides (e.g., ⁶⁸Ga and ¹⁸F) to enable rapid pharmacokinetics and same-day imaging protocols. Emerging platforms such as affibodies and aptamers offer further advantages in target affinity and reduced immunogenicity. However, clinical translation requires rigorous validation: larger, histologically confirmed cohorts, head-to-head comparison with CT/MRI, and correlation with hard clinical endpoints. Moreover, leveraging GPC3 expression as a biomarker could guarantee a deeper knowledge of tumor biology—differentiation grade and vascular invasion risk—and guide theranostic strategies. While β-emitters (⁹⁰Y, ¹⁷⁷Lu) have been explored for GPC3-directed therapy, their efficacy is influenced by oxygenation and cell-cycle status, whereas α-emitters (²²⁵Ac) may overcome these constraints, albeit with challenges in radionuclide selection and daughter nuclide management. Finally, dual-targeting probes combining GPC3 and prostate-specific membrane antigen (PSMA) have demonstrated superior uptake and retention in murine models, suggesting a versatile approach for future clinical diagnostics and therapy planning. Full article

Immunotherapy has revolutionized cancer treatment; however, the availability of cost-effective blood-based biomarkers for prognostic and predictive factors of immune treatment in patients with solid tumors remains limited. Due to low cost and easy accessibility, blood-based biomarkers should constitute an essential component of studies to optimize and monitor immunotherapy. Currently available markers that can be measured in peripheral blood include total monocyte count, myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), relative eosinophil count, cytokine levels (such as IL-6, IL-8, and IL-10), lactate dehydrogenase (LDH), C-reactive protein (CRP), soluble forms of CTLA-4 and PD-1 or PD-L1, as well as circulating tumor DNA (ctDNA). In our mini-review, we discuss the latest evidence indicating that routinely accessible peripheral blood parameters—such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and rheological parameters, which so far have been rarely considered for such an application, may be used as non-invasive biomarkers in cancer immunotherapy. Rheological parameters such as whole blood viscosity are influenced by several factors, such as hematocrit, aggregability and deformability of erythrocytes, and plasma viscosity, which is largely dependent on plasma proteins. Especially in cases where the set of symptoms indicates a high probability of hyperviscosity syndrome, blood rheological tests can lead to early diagnosis and treatment. Both biochemical and rheological parameters are prone to become novel and future standards for assessing immunotherapy among patients with solid tumors. Full article

Background/Objectives: Pancreatic cancer (PC) is among the most aggressive malignancies, often diagnosed at late stages. MicroRNAs (miRNAs) and proteins released from the tumor microenvironment into body fluids represent promising non-invasive biomarkers for early cancer detection. In this study, we took advantage of an innovative ultrasound (US)-based instrument (SonoWell^®, Inno-Sol srl, Rome, Italy) to treat PC cells in order to promote and amplify the release of molecules, with the aim of identifying novel putative diagnostic PC biomarkers. Methods: Three human pancreatic adenocarcinoma cell lines (T3M-4, Panc02.03, and PaCa-44) and a non-cancerous pancreatic epithelial line (HPanEPic) were subjected to US using the SonoWell instrument. MiRNAs released in the supernatants were profiled by TaqMan-based qRT-PCR microfluidic cards, while proteins were analyzed by antibody arrays. Publicly available datasets of circulating miRNAs in PC patients were also reviewed. Results: Expression levels of 22 miRNAs in T3M-4 cells, 11 in Panc02.03, and 22 in PaCa-44, none of which were identified in the non-cancerous cell line profiling, were increased in the supernatant of US-treated as opposed to control cells. Among the statistically significant miRNAs or miRNAs common to at least two tumor cell lines, the expression levels of miR-155-5p, miR-320a, miR-32-5p, and miR-93-5p were also found to be significantly upregulated in sera from PC patients compared to the results for healthy controls. With regard to proteins released after sonication, several molecules were identified as candidate biomarkers in cancer US supernatants (Beta-2 microglobulin, CA125, CA19-9, CEA, CRP, Galectin-3, TIMP-1, uPA, and VEGF-A). Conclusions: We demonstrated that US-mediated sonoporation can promote and amplify the release of small molecules, miRNAs, and proteins into cell culture supernatants for consideration as putative biomarkers, thus encouraging further studies aimed at directly validating their expression levels in sera/plasma from PC patients and at deepening their role in the treatment of PC. Full article

Circulating free DNA (cfDNA) is genetic material released from various cells into bodily fluids. Among its fractions, circulating tumor DNA (ctDNA) originates from tumor cells and reflects their genetic material, including mutations and epigenetic changes. Methods commonly employed for detecting ctDNA in blood include next-generation sequencing (NGS) and various types of PCR. The presence of ctDNA can be utilized in liquid biopsies for many diagnostic purposes related to various cancers. It is a minimally invasive method of sampling molecular compounds from tumor cells. In this paper, we focus on current knowledge regarding the liquid biopsy of blood ctDNA in the context of lung cancer, one of the leading causes of cancer-related mortality. Currently, as a clinically approved method, liquid biopsy serves as a complementary technique in NSCLC diagnostic and genetic profiling. Other applications of liquid biopsy that are still being investigated include the detection of minimal residual disease (MRD) after curative treatment and response monitoring to systemic treatment. This review discusses current and future potential directions for the development and implementation of ctDNA for patients with NSCLC. Full article

Muscle-invasive bladder cancer (MIBC) is a biologically aggressive disease with high recurrence rates, despite advances in surgical and systemic therapies. Circulating tumor DNA (ctDNA), a tumor-specific fraction of cell-free DNA, has emerged as a promising non-invasive biomarker for the real-time assessment of tumor burden, treatment response, and minimal residual disease (MRD). This review explores the biological basis, detection technologies, and clinical utility of ctDNA in MIBC, highlighting its role in preoperative risk stratification, postoperative surveillance, and personalized decision-making for adjuvant and systemic therapies. We critically examine current evidence from pivotal trials and ongoing studies that support ctDNA’s prognostic and predictive value. Additionally, we discuss emerging applications, including ctDNA-guided immunotherapy, integration with imaging and molecular data, and potential to inform bladder-sparing strategies. While ctDNA presents technical and logistical challenges, its incorporation into prospective clinical workflows promises to enhance precision oncology and improve outcomes in patients with MIBC. Full article

Early detection of cancer is crucial for improving patient outcomes. Traditional modalities such as mammography and low-dose computed tomography are effective but exhibit inherent limitations, including radiation exposure and accessibility challenges. This review explores innovative, non-invasive cancer screening methods, focusing on liquid biopsy and volatile organic compound (VOC)-based detection platforms. Liquid biopsy analyzes circulating tumor DNA and other biomarkers in bodily fluids, offering potential for early detection and monitoring of treatment response. VOC-based detection leverages unique metabolic signatures emitted by cancer cells, detectable in exhaled breath or other bodily emissions, providing a rapid and patient-friendly screening option. We provide a comprehensive overview of these advanced multi-cancer detection techniques to enhance diagnostic accuracy, accessibility, and patient adherence, and ultimately enhance survival rates and patient outcomes. Full article

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, emphasizing the urgent need for reliable biomarkers for early diagnosis and prognosis. MicroRNA-141 (miR-141) is a small non-coding RNA molecule that plays a regulatory role in cell proliferation and differentiation and has been linked to various types of cancer. Objective: This study aims to evaluate the clinical and prognostic relevance of circulating levels of miR-141 in untreated patients with CRC. Method: A total of 40 patients with CRC and 20 healthy subjects matched for age and sex were selected for this study. Blood samples from these individuals were analyzed using real-time PCR to determine the levels of miR-141. Results: Despite the absence of any substantial correlations between levels of miR-141 and conventional prognostic factors, including disease stage, lymph node involvement, vascular/perineural invasion, or metastasis, a statistically significant correlation was identified between miR-141 levels and the extent of local tumor invasion (T stage) (p = 0.034). These findings suggest that microRNA-141 may be involved in local tumor infiltration and warrant further validation in larger, multicenter studies. Conclusions: Although miR-141 alone may not serve as a definitive biomarker for CRC diagnosis or prognosis, its potential role—particularly in combination with other markers—could contribute to refined risk stratification strategies in CRC management. Full article

Background: Circulating tumor cells (CTCs) are a rare population of cells considered the seeds of metastasis, detectable in the bloodstream of patients with solid tumors. In breast cancer (BC) their prognostic value is established in the metastatic setting but remains uncertain in early-stage disease. This study provides a 10-year follow-up analysis of disease-free survival (DFS) in a previously described cohort of early-stage BC patients, aiming to evaluate the long-term prognostic significance of CTC detection. Methods: As reported in a previous study, 48 patients with stage I–II operable BC were enrolled. CTCs were isolated from peripheral blood using an EpCAM-independent enrichment method followed by DEPArray analysis at baseline (pre-surgery) and six months post-surgery. CTC positivity was defined as the presence of ≥1 CTC. DFS outcomes were assessed over a 10-year follow-up period, and statistical analyses were performed using Kaplan–Meier survival estimates and log-rank tests. Results: After 10 years, 3 patients (6.3%) experienced disease relapse, and 2 developed lymphomas. No statistically significant association was observed between CTC presence—either pre-surgery (p = 0.13) or post-surgery (p = 0.25)—and DFS. Overall, the detection of CTCs using this method did not reliably predict long-term outcomes in this cohort. Conclusions: CTC enumeration before and after surgery does not appear to be a reliable prognostic marker for long-term DFS in early-stage BC. Although associated with specific pathological features such as vascular invasion, the role of CTC analysis in this setting remains limited by methodological challenges and cost. Larger, standardized studies are needed to validate the prognostic relevance of conventional and non-conventional CTC populations in early BC. Full article

Liquid biopsy has gained attention in oncology as a non-invasive diagnostic tool, offering valuable insights into tumor biology through the analysis of circulating nucleic acid (cfDNA and cfRNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), and tumor-educated platelets (TEPs). In this review, we summarize the clinical use of liquid biopsies in cancer now and look forward to its future, with a particular emphasis on some the methods used to isolate the liquid biopsy analytes. This technique provides real-time information on tumor dynamics, treatment response, and disease progression, with the potential for early diagnosis and personalized treatment. Despite its advantages, liquid biopsy faces several challenges, particularly in detecting analytes in early-stage cancers and evaluating the tumor molecular fraction. Tumor burden, molecular fraction, and the presence of subclones can impact the sensitivity and specificity of the analysis. Recent advancements in artificial intelligence (AI) have enhanced the diagnostic accuracy of liquid biopsy by integrating data, and multimodal approaches that combine multiple biomarkers such as ctDNA, CTCs, EVs, and TEPs show promise in providing a more comprehensive view of tumor characteristics. Liquid biopsy has the potential to revolutionize cancer care by providing rapid, non-invasive, and cost-effective diagnostics, enabling timely interventions and personalized treatment strategies. Full article

Background/Objectives: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for non-invasive tumor monitoring in diffuse large B-cell lymphoma (DLBCL). Methods: In this study, 52 patients with newly diagnosed advanced-stage DLBCL treated with R-CHOP underwent serial ctDNA analysis at baseline, interim (after three cycles), and end of treatment. The prognostic significance of ctDNA dynamics was evaluated, and its predictive value was compared with the PET/CT response. Results: Targeted next-generation sequencing revealed baseline ctDNA in 98.1% of patients, with 74.7% concordance to tumor tissue genotyping. Higher baseline ctDNA levels correlated with elevated LDH, older age, and high IPI scores. A ≥2-log reduction in ctDNA at interim was significantly associated with improved overall survival (p = 0.004), though not with progression-free survival. Notably, combining interim ctDNA dynamics with PET/CT results enhanced the predictive accuracy for treatment outcomes, particularly among patients with partial metabolic responses. Conclusions: These findings support the clinical utility of ctDNA for dynamic risk assessment in DLBCL, and suggest that integrating ctDNA with imaging biomarkers may guide more personalized therapeutic strategies. Further validation using highly sensitive ctDNA assays is warranted to optimize its role in routine clinical practice. Full article

Liquid biopsy through the analysis of circulating tumor DNA (ctDNA) is emerging as a powerful and non-invasive tool complementing tissue biopsy in lymphoma management. Whilst tissue biopsy remains the diagnostic gold standard, it fails to detect the molecular heterogeneity of the tumor’s multiple compartments and poses challenges for sequential disease monitoring. In diffuse large-B-cell lymphoma (DLBCL), ctDNA facilitates non-invasive genotyping by identifying hallmark mutations (e.g., MYD88, CD79B, EZH2), enabling molecular cluster classification. Dynamic changes in ctDNA levels during DLBCL treatment correlate strongly with progression-free survival and overall survival, underscoring its value as a predictive and prognostic biomarker. In Hodgkin’s lymphoma, characterized by a scarcity of malignant cells in tissue biopsies, ctDNA provides reliable molecular insights into tumor biology, response to therapy, and relapse risk. In primary central nervous system lymphoma, the detection of MYD88 L265P in ctDNA offers a highly sensitive, specific, and minimally invasive diagnostic option. Likewise, in aggressive T-cell lymphomas, ctDNA supports molecular profiling, aligns with tumor burden, and shows high concordance with tissue-based results. Ongoing and future clinical trials will be critical for validating and standardizing ctDNA applications, ultimately integrating liquid biopsy into routine clinical practice and enabling more personalized and dynamic lymphoma care. Full article

Identifying prognostic markers in colorectal cancer (CRC) is crucial for improving treatment outcomes. Although carcinoembryonic antigen (CEA) is recommended in the guidelines of the National Comprehensive Cancer Network, its sensitivity and specificity are inconsistent, limiting its utility in patients with normal CEA levels. Circulating tumor cells (CTCs), including those expressing CD133—a cancer stem cell marker involved in tumor progression and therapy resistance—are associated with metastasis and survival outcomes. This study evaluated the prognostic significance of CD133-positive CTCs, and their combined effect with CEA, in patients with CRC. Peripheral blood samples from 195 patients with CRC (stages I–IV) were analyzed. CTCs were isolated using OncoQuick tubes and CD133 mRNA expression was detected by reverse transcription polymerase chain reaction. In clinicopathological analysis, CD133-positive CTCs were detected in 27.2% of cases, correlating with serosal invasion (p = 0.016). Multivariate Cox analysis showed that CD133-positive CTCs were associated with worse disease-specific survival (p = 0.001). Patients with CD133-positive CTCs and CEA ≥ 5 ng/mL (high CEA) had a significantly poorer prognosis (p < 0.001), whereas those with CD133-negative CTCs and CEA < 5 ng/mL (low CEA) had a better prognosis (p = 0.039). CD133 expression in CTCs, especially in combination with CEA, may serve as a valuable prognostic marker in CRC. Full article