Search Results (112)

Oral cancer, the most common form of head and neck cancer, is worldwide a serious public health problem. Most patients present a locally advanced disease, and face poor prognosis, even with multimodality treatment. They may also develop second primary tumors in the entirety of their upper aerodigestive tract. The most altered signaling pathways are the PI3K/AKT/mTOR, TP53, RB, and the WNT/β-catenin pathways. Genomic and molecular cytogenetic analyses have revealed frequent losses at 3p, 8p, 9p, and 18q, along with gains at 3q, 7p, 8q, and 11q, and several genes frequently affected have been identified, such as TP53, CCND1, CTTN, CDKN2A, EGFR, HRAS, PI3K, ADAM9, MGAM, SIRPB1, and FAT1, among others. Various epigenetic alterations were also found, such as the global hypomethylation and hypermethylation of CDKN2A, APC, MGMT, PTEN, CDH1, TFP12, SOX17, GATA4, ECAD, MGMT, and DAPK. Several microRNAs are upregulated in oral cancer, including miR-21, miR-24, miR-31, miR-184, miR-211, miR-221, and miR-222, while others are downregulated, such as miR-203, miR-100, miR-200, miR-133a, miR-133b, miR-138, and miR-375. The knowledge of this molecular pathogenesis has not yet been translated into clinical practice, apart from the use of cetuximab, an EGFR antibody. Oral tumors are also genetically heterogenous and affect several pathways, which means that, due to the continuous evolution of these genetic alterations, a single biopsy is not sufficient to fully evaluate the most adequate molecular targets when more drugs become available. Liquid biopsies, either resorting to circulating tumor cells, extracellular vesicles or cell-free nucleic acids, have the potential to bypass this problem, and have potential prognostic and staging value. We critically review the current knowledge on the molecular, genetic and epigenetic alterations in oral cancer, as well as the applications and challenges of liquid biopsies in its diagnosis, follow-up, and prognostic stratification. 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

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

Glioblastoma (GBM) is the most prevalent and aggressive primary central nervous system (CNS) tumor in adults. GBMs exhibit genetic and epigenetic heterogeneity, posing difficulties in surveillance and being associated with high rates of recurrence and mortality. Nevertheless, due to the high infiltrating ability of glioblastoma cells, and regardless of the considerable progress made in radiotherapeutic, chemotherapeutic, and surgical protocols, the treatment of GBM is still inefficient. Conventional diagnostic approaches, such as neuroimaging techniques and tissue biopsies, which are invasive maneuvers, present certain challenges and limitations in providing real-time information, and are incapable of differentiating pseudo-progression related to treatment from real tumor progression. Liquid biopsy, the analysis of biomarkers such as nucleic acids (DNA/RNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), or tumor-educated platelets (TEPs) that are present in body fluids, provides a minimally invasive and dynamic method of diagnosis and continuous monitoring for GBM. It represents a new preferred approach that enables a superior manner to obtain data on possible tumor risk, prognosis, and recurrence assessment. This article is a literature review that aims to provide updated information about GBM biomarkers in body fluids and to analyze their clinical efficiency. Full article

Breast cancer is an aggressive disease of multiple subtypes with varying phenotypic, hormonal, and clinicopathological features, offering enhanced resistance to conventional therapeutic regimens. There is an unmet need for reliable molecular biomarkers capable of detecting the malignant transformation from the early stages of the disease to enhance diagnosis and treatment outcomes. A subset of small non-coding nucleic acid molecules, micro ribonucleic acids (microRNAs/miRNAs), have emerged as promising biomarkers due to their role in gene regulation and cancer pathogenesis. This review discusses, in detail, the different origins and hormone-like regulatory functionalities of miRNAs localized in tumor tissue and in the circulation, as well as their inherent stability and turnover that determines the utility of miRNAs as biomarkers for disease detection, monitoring, prognosis, and therapeutic targets. Full article

Thyroid cancer is the most prevalent endocrine cancer. The prognosis depends on the type and stage at diagnosis. Thyroid cancer treatments involve surgery, possibly followed by additional therapeutic options such as hormone therapy, radiation therapy, targeted therapy and chemotherapy. Besides the well-known thyroid tumor biomarkers, new circulating biomarkers are now emerging. Advances in genomic, transcriptomic and proteomic technologies have allowed the development of novel tumor biomarkers. This review explores the current literature data to critically analyze the benefits and limitations of routinely measured circulating biomarkers for the diagnosis and monitoring of thyroid cancer. The review also sheds light on new circulating biomarkers, focusing on the challenges of their use in the clinical management of thyroid cancer, underlining the need for the identification of a new generation of circulating biomarkers. Full article

This review evaluates the advances in the early detection and diagnosis of endometrial cancer (EC), emphasizing the growing importance of minimally invasive techniques and novel biomarkers. Current diagnostic protocols for EC rely heavily on invasive procedures such as transvaginal ultrasound (TVU), hysteroscopy, and endometrial biopsy, which, although effective, can be overly burdensome for patients and inefficient for asymptomatic or low-risk populations. As there is no consensus on EC screening in high-risk or general populations, recent studies have explored alternative methods using biofluids and genomic biomarkers to improve sensitivity and specificity and facilitate access for patients. This review summarizes findings on DNA methylation markers, circulating tumor-derived nucleic acids, and the potential of liquid biopsy approaches for the early detection of EC. These innovations may not only streamline screening but also reduce the need for invasive procedures. This review highlights the potential of these biomarkers to be integrated seamlessly into the existing cervical cancer screening programs, which could transform screening methods for endometrial cancer and support the development of personalized, less invasive diagnostic procedures. Full article

Circulating tumor cells and cell-free nucleic acids are novel diagnostic, prognostic and predictive tools for non-invasive and cost-effective cancer detection in liquid biopsy. Carbonic anhydrase IX (CAIX) has been proposed as a biomarker in urogenital tumors and urine sediment. Our aim was to evaluate CAIX full-length percentage (CAIX FL%) in urine-cell-free RNA (cfRNA) and its relationship with tumor-cell-associated RNA (TC-RNA). CAIX FL% was quantified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in patients with prostate, kidney or bladder carcinoma. When cfRNA and TC-RNA were analyzed, CAIX FL% was significantly higher in urine samples from cancer patients than from controls. Using a 10% cutoff for CAIX FL%, specificity, sensitivity, positive and negative predictive values, as well as accuracy for TC-RNA were higher than for cfRNA in all urogenital cancers, but varied according to tumor type. CAIX FL% distribution in TC-RNA differed significantly (p < 0.001) between control and tumor samples (37.5% and 96.2%, respectively); similar results were obtained for each tumor type. Additionally, the 10% cutoff showed a 77.9% concordance between TC-RNA and cfRNA. In conclusion, urine is proposed as an alternative biofluid for investigating CAIX FL% in urogenital cancers, and this parameter can be reliably measured as cfRNA and TC-RNA with different predictive capabilities depending on tumor type. Full article

Sarcomas are a heterogeneous group of malignancies with a high mortality rate. Detection of circulating tumor-derived material, such as circulating RNA in the peripheral blood of patients, has shown to be useful in diagnosis, prediction of prognosis and disease monitoring in several malignancies. This systematic review aims to probe the existing methods for detecting circulating tumor-derived RNAs from patients affected by sarcoma and their possible clinical application. A systematic review of the literature indexed in PubMed was performed. Each article had to analyze circulating RNA in human specimens obtained from liquid biopsies of patients affected by sarcoma. A total of 26 articles were included. We evaluated 1381 patients; 72% were affected by bone sarcoma and 28% by soft tissue sarcoma. By PCR-based methods, all the studies investigated circulating tumor RNA, mostly in the peripheral blood. Nearly half of the authors investigated the tumor expression and/or release of miRNA (42%). Several authors pointed out that circulating tumor-derived RNA has proven to have potential application in a clinical setting for sarcomas. To the best of our knowledge, this is the first review in the literature to attempt to put together data specifically on ctRNA in patients affected by sarcoma. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally. Most patients present with late diagnosis, leading to poor prognosis. This narrative review explores novel biomarkers for early HCC detection. We conducted a comprehensive literature review analyzing protein, circulating nucleic acid, metabolite, and quantitative proteomics-based biomarkers, evaluating the advantages and limitations of each approach. While established markers like alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, and AFP-L3 remain relevant, promising candidates include circulating tumor DNA, microRNAs, long noncoding RNAs, extracellular vesicle, and metabolomic biomarkers. Multi-biomarker panels like the GALAD score, Oncoguard, and Helio liver test show promise for improved diagnostic accuracy. Non-invasive approaches like urine and gut microbiome analysis are also emerging possibilities. Integrating these novel biomarkers with current screening protocols holds significant potential for earlier HCC detection and improved patient outcomes. Future research should explore multi-biomarker panels, omics technologies, and artificial intelligence to further enhance early HCC diagnosis and management. Full article

Background: Liquid biopsy is a method that could potentially improve the management of thyroid cancer (TC) by enabling the detection of circulating tumor DNA and RNA (ctDNA, ctRNA). The BRAF^V600E mutation appears to be the most representative example of a biomarker in liquid biopsy, as it is the most specific mutation for TC and a target for molecular therapeutics. The aim of this review is to summarize the available data on the detection of the BRAF^V600E mutation in liquid biopsy in patients with TC. Methods: A comprehensive analysis of the available literature on the detection of the BRAF^V600E mutation in liquid biopsy in TC was performed. Thirty-three papers meeting the inclusion criteria were selected after full-text evaluation. Results: Eleven papers discussed correlations between BRAF mutation and clinicopathological characteristics. Nine studies tested the utility of BRAF^V600E detection in the assessment of residual or recurrent disease. Seven studies investigated BRAF-mutated circulating tumor nucleic acids (ctNA) as a marker of response to targeted therapy. In seven studies the method did not detect the BRAF^V600E mutation. Conclusions: This review shows the potential of BRAF^V600E-mutated ctNA detection in monitoring disease progression, particularly in advanced TC. The diagnostic value of BRAF^V600E-mutated ctNA detection appears to be limited to advanced TC. The choice of the molecular method (quantitative PCR [qPCR], droplet digital polymerase chain reaction [ddPCR], and next-generation sequencing [NGS]) should be made based on the turnaround time, sensitivity of the test, and the clinical indications. Despite the promising outcomes of some studies, there is a need to verify these results on larger cohorts and to unify the molecular methods. Full article

Invasion and metastasis are important hallmarks of lung cancer, and affect patients’ survival. Early diagnostics of metastatic potential are important for treatment management. Recent findings suggest that the transition to an invasive phenotype causes changes in the expression of 700–800 genes. In this context, the biomarkers restricted to the specific type of cancer, like lung cancer, are often overlooked. Some well-known protein biomarkers correlate with the progression of the disease and the immunogenicity of the tumor. Most of these biomarkers are not exclusive to lung cancer because of their significant role in tumorigenesis. The dysregulation of others does not necessarily indicate cell invasiveness, as they play an active role in cell division. Clinical studies of lung cancer use protein biomarkers to assess the invasiveness of cancer cells for therapeutic purposes. However, there is still a need to discover new biomarkers for lung cancer. In the future, minimally invasive techniques, such as blood or saliva analyses, may be sufficient for this purpose. Many researchers suggest unconventional biomarkers, like circulating nucleic acids, exosomal proteins, and autoantibodies. This review paper aims to discuss the advantages and limitations of protein biomarkers of invasiveness in lung cancer, to assess their prognostic value, and propose novel biomarker candidates. Full article

Liquid biopsy has emerged as a promising noninvasive approach for colorectal cancer (CRC) management. This review focuses on technologies detecting circulating nucleic acids, specifically circulating tumor DNA (ctDNA) and circulating RNA (cfRNA), as CRC biomarkers. Recent advancements in molecular technologies have enabled sensitive and specific detection of tumor-derived genetic material in bodily fluids. These include quantitative real-time PCR, digital PCR, next-generation sequencing (NGS), and emerging nanotechnology-based methods. For ctDNA analysis, techniques such as BEAMing and droplet digital PCR offer high sensitivity in detecting rare mutant alleles, while NGS approaches provide comprehensive genomic profiling. cfRNA detection primarily utilizes qRT-PCR arrays, microarray platforms, and RNA sequencing for profiling circulating microRNAs and discovering novel RNA biomarkers. These technologies show potential in early CRC detection, treatment response monitoring, minimal residual disease assessment, and tumor evolution tracking. However, challenges remain in standardizing procedures, optimizing detection limits, and establishing clinical utility across disease stages. This review summarizes current circulating nucleic acid detection technologies, their CRC applications, and discusses future directions for clinical implementation. Full article

Immunotherapy combats tumors by enhancing the body’s immune surveillance and clearance of tumor cells. Various nucleic acid drugs can be used in immunotherapy, such as DNA expressing cytokines, mRNA tumor vaccines, small interfering RNAs (siRNA) knocking down immunosuppressive molecules, and oligonucleotides that can be used as immune adjuvants. Nucleic acid drugs, which are prone to nuclease degradation in the circulation and find it difficult to enter the target cells, typically necessitate developing appropriate vectors for effective in vivo delivery. Biomimetic drug delivery systems, derived from viruses, bacteria, and cells, can protect the cargos from degradation and clearance, and deliver them to the target cells to ensure safety. Moreover, they can activate the immune system through their endogenous activities and active components, thereby improving the efficacy of antitumor immunotherapeutic nucleic acid drugs. In this review, biomimetic nucleic acid delivery systems for relieving a tumor immunosuppressive microenvironment are introduced. Their immune activation mechanisms, including upregulating the proinflammatory cytokines, serving as tumor vaccines, inhibiting immune checkpoints, and modulating intratumoral immune cells, are elaborated. The advantages and disadvantages, as well as possible directions for their clinical translation, are summarized at last. Full article

Gliomas, particularly glioblastoma (GBM), represent the most prevalent and aggressive tumors of the central nervous system (CNS). Despite recent treatment advancements, patient survival rates remain low. The diagnosis of GBM traditionally relies on neuroimaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scans and postoperative confirmation via histopathological and molecular analysis. Imaging techniques struggle to differentiate between tumor progression and treatment-related changes, leading to potential misinterpretation and treatment delays. Similarly, tissue biopsies, while informative, are invasive and not suitable for monitoring ongoing treatments. These challenges have led to the emergence of liquid biopsy, particularly through blood samples, as a promising alternative for GBM diagnosis and monitoring. Presently, blood and cerebrospinal fluid (CSF) sampling offers a minimally invasive means of obtaining tumor-related information to guide therapy. The idea that blood or any biofluid tests can be used to screen many cancer types has huge potential. Tumors release various components into the bloodstream or other biofluids, including cell-free nucleic acids such as microRNAs (miRNAs), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), proteins, extracellular vesicles (EVs) or exosomes, metabolites, and other factors. These factors have been shown to cross the blood-brain barrier (BBB), presenting an opportunity for the minimally invasive monitoring of GBM as well as for the real-time assessment of distinct genetic, epigenetic, transcriptomic, proteomic, and metabolomic changes associated with brain tumors. Despite their potential, the clinical utility of liquid biopsy-based circulating biomarkers is somewhat constrained by limitations such as the absence of standardized methodologies for blood or CSF collection, analyte extraction, analysis methods, and small cohort sizes. Additionally, tissue biopsies offer more precise insights into tumor morphology and the microenvironment. Therefore, the objective of a liquid biopsy should be to complement and enhance the diagnostic accuracy and monitoring of GBM patients by providing additional information alongside traditional tissue biopsies. Moreover, utilizing a combination of diverse biomarker types may enhance clinical effectiveness compared to solely relying on one biomarker category, potentially improving diagnostic sensitivity and specificity and addressing some of the existing limitations associated with liquid biomarkers for GBM. This review presents an overview of the latest research on circulating biomarkers found in GBM blood or CSF samples, discusses their potential as diagnostic, predictive, and prognostic indicators, and discusses associated challenges and future perspectives. Full article