Search Results (1,802)

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Background: Second-generation androgen receptor signaling inhibitors are one of the main treatment options in metastatic castration-resistant prostate cancer (mCRPC). Nonetheless, a considerable proportion show limited response to treatment, which indicates the need for convenient, easily accessible predictor biomarkers, a role suited for liquid biopsy. Methods: We conducted a PRISMA-compliant systematic review of four databases (Embase, Medline, Scopus, Web of Science) to identify all studies (observational studies and clinical trials) investigating cell-free DNA, circulating tumor cells, exosomes, and circulating RNAs as prognostic markers in metastatic castration-resistant patients starting androgen receptor signaling inhibitors. We excluded studies that evaluated combination therapies, rare histological subtypes or included nonmetastatic or castrate-sensitive disease. We also evaluated whether published papers followed reporting guidelines (REMARK, STROBE, or CONSORT for abstracts). Results: We identified a total of 123 reports, from which we identified only a few well-studied and consistent biomarkers: androgen receptor overexpression/copy number gain and splice variant 7, as well as disease burden markers (circulating tumor DNA fraction and circulating tumor cell concentration). Alterations or copy number loss in tumor suppressors PTEN, RB1, and TP53 were second in terms of quantity and consistency of evidence. However, a large majority of identified biomarkers were relatively understudied or inconsistent. We identified two potential vulnerabilities: inconsistent adherence to reporting guidelines and the under-inclusion of patients of non-Western European ancestry. Conclusions: A large number of biomarkers were linked to worse outcomes in prostate cancer; nonetheless, in most cases, the evidence is limited or inconsistent, or even contradictory. The main exceptions pertain to androgen receptor signaling and disease burden, and, to a smaller extent, to certain tumor suppressor genes. Further studies are needed to confirm their clinical utility, using clear and consistent methodologies and including patients from currently understudied populations. Full article

Background/Objectives: Emerging studies have indicated the importance of intra-tumoral neuronal signals in tumor progression and immune modulation. However, there is limited insight into neuroimmune crosstalk, and the molecules involved are largely unknown. This study investigates the relationship between tumor-derived neuropeptides and immune modulation in head and neck squamous cell carcinoma (HNSC). Methods: By utilizing neuropeptide databases and web tools leveraging TCGA data, neuropeptides’ expression and their associations with neurotrophic factors, immune cell infiltration, and immune checkpoints were analyzed, followed by survival analysis. Results: Over half of the neuropeptides were expressed in HNSC, with 16% exhibiting differential expression compared to normal counterparts. Notably, differentially expressed neuropeptides showed significant correlations with neurotrophic factors, immune cell infiltration, and checkpoint genes. Further, their expression was significantly different in responder and non-responder patient samples subjected to immune checkpoint therapy. Neuropeptide genes—PTHLH, NMB, GAST, APLN, and LYNX1—were identified and emerged as crucial mediators in neuroimmune crosstalk. Additionally, the neurotrophic gene NTRK1 exhibited extensive correlation with immune checkpoint genes, underscoring the prevalence of neuroimmune crosstalk in HNSC. Conclusions: These findings shed light on the role of tumor-derived neuropeptides in neuroimmune regulation in HNSC, offering valuable insights for future studies to decode the cancer neuroscience of HNSC progression and therapy. Full article

Background: We investigated the role of a high-sensitive cardiac troponin T (hsTnT) increase below the upper limit of normal (ULN) in patients with breast cancer (BC). hsTnT assays accurately quantify very low plasma troponin concentrations and enable the early detection of cardiomyocyte injury before a drop in the left ventricular ejection fraction (LVEF). The increase in hsTnT below the ULN in response to chemotherapy has not previously been studied. Method: This was an open-label pilot study. Female patients with newly diagnosed BC scheduled to receive systemic cancer treatment were recruited. Blood sampling and echocardiography were performed at baseline, at 3 and 6 months of cancer treatment. hsTnT concentrations were measured using the Elecsys TnT hs assay (Roche Diagnostics). The limit of blank and 99th percentile cutoff values for the hsTnT assay were 3 and 14 ng/L. We calculated the rise in hsTnT (ΔhsTnT) by the difference (%) between its baseline level and during follow-up (FU) in each patient. Results: Among eligible subjects, we excluded 4 patients before the start of treatment and 17 patients during the follow-up with values for the hsTnT >14 ng/L. Finally, 60 women with a median age of 48.6 ± 1.3 years were included in the study. The median baseline hsTnT concentration was 5.5 ± 1.4 ng/L. During 6 months of cancer treatment, hsTnT increased in all patients by up to 10–305% from baseline, with an average of 94.2%. LV EF was normal at baseline and decreased significantly compared to the value before cancer treatment (61.9 ± 3.3% vs. 56.3 ± 7.0%; p < 0.045). We correlated the hsTnT rise with a drop in LV EF ≥ 10% from its baseline level. Logistic regression analysis showed that Δ hsTnT has a good predictive value for LV dysfunction, 0.78 (p = 0.05), 95% CI (0.67–0.90). The increase in hsTnT > 81% was determined as the optimal threshold value for detecting early biochemical cardiotoxicity. Conclusion: It was investigated that hsTnT rise within the cutoff < 14 ng/L can be used as a marker of early biochemical cardiotoxicity and is valuable for predicting LV drop in 6 months of FU. We conclude that BC patients with increased hsTnT plasma concentration > 81% from the baseline value should be considered as high-risk patients for cardiotoxicity and need more precise cardiac monitoring and early preventive medical intervention strategies. Full article

Background/Objective: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has affected more than 1700 women with textured breast implants. About 80% of patients present with fluid (seroma) around their implant. BIA-ALCL can be cured by surgery alone when confined to the seroma and lining of the peri-implant capsule. To address the need for early detection, we developed a rapid point of care (POC) lateral flow assay (LFA) to identify lymphoma in seromas. Methods: We compared 28 malignant seromas to 23 benign seromas using both ELISA and LFA. LFA test lines (TL) and control lines (CL) were visualized and measured with imaging software and the TL/CL ratio for each sample was calculated. Results: By visual exam, the sensitivity for detection of CA9 was 93% and specificity 78%, while the positive predictive value was 84% and negative predictive value 90%. Quantitative image analysis increased the positive predictive value to 96% while the negative predictive value reduced to 79%. Conclusions: We conclude that CA9 is a sensitive biomarker for detection and screening of patients for BIA-ALCL in patients who present with seromas of unknown etiology. The CA9 LFA can potentially replace ELISA, flow cytometry and other tests requiring specialized equipment, highly trained personnel, larger amounts of fluid and delay in diagnosis of BIA-ALCL. Full article

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

Background: Tumors of the pleura, such as metastatic lung cancer and mesothelioma, are amongst the most lethal and therapy-resistant tumors. The first manifestation of the disease is often pleural effusion, the first available material for diagnosis. The five-year survival rate is exceptionally low, around 10–20%, and only a small proportion of patients harbor mutations that allow targeted treatments. Almost all patients develop resistance to treatment, which is often palliative. There is therefore an urgent need to refine the selection of drugs and patients for personalized treatment. Methods: We isolated and cultured cells from pleural effusions in 3D cell aggregates and compared their drug sensitivity ex vivo to the clinical response to the same chemotherapeutic agents, combined with targeted sequencing and network analysis. Results: The ex vivo drug response showed a positive correlation with the treatment response and survival of patients in the clinic, with a stronger link to overall survival than to progression-free survival. Cryopreserved cells showed a similar response to freshly collected cells from the clinic. Conclusions: The findings advance the field of ex vivo screening and present an opportunity to combine strategies for functional precision medicine with comprehensive characterization of disease for improved treatment and future management of lung cancer. Full article

Background: Pancreatic cancer is frequently identified as the cancer type with the shortest probable survival time after diagnosis, and efforts to develop successful treatments have had a very limited impact in the clinic. One reason for the limited therapeutic options is the lack of appealing drug targets. The great majority of pancreatic cancers are classified as Pancreatic Ductal Adenocarcinoma (PDAC), in which the genetic landscape is dominated by four genes: KRAS, TP53, CDKN2A, and SMAD4. However, despite extensive knowledge of these genetic drivers, the development of effective therapies has seen only very limited success. Methods: Existing evidence indicates that mutations in the tumour suppressor gene PTEN are uncommon in PDAC (<10% cases). However, the loss of PTEN function through non-genetic mechanisms may be much more common and have a strong impact. We therefore summarise and review a large body of immunohistochemical studies that address the loss of PTEN in PDAC as well as a smaller number of studies addressing other implicated proteins, including KDM6A and ARID1A. Results: These studies show some loss of PTEN protein in more than half of PDAC cases. Furthermore, although genetic changes in genes including KDM6A/UTX and ARID1A are also uncommon, reduced expression of their encoded proteins is observed in many, perhaps most, cases of PDAC. Conclusions: These analyses, which go beyond genetics, highlight the broader set of cellular functions that are dysregulated in many pancreatic cancers and provide broader opportunities for treatment strategies. This review highlights the emerging importance of other drivers in PDAC, which are less well-studied in this context. Full article

Background: PTEN is a tumor suppressor that controls many pathophysiological pathways, including cell proliferation, differentiation, apoptosis and invasiveness. Although PTEN down-modulation is a critical event in neoplastic progression, it becomes apparent that transient and local inhibition of PTEN activity might be beneficial for the healing process. Methods: In the present study, we investigated the impact of PTEN invalidation in mouse intestinal epithelium under a physiological condition and after dextran sulfate sodium (DSS) treatment to induce experimental colitis. PTEN conditional knockout was induced in intestinal epithelial cells after crossing villin-Cre and PTEN^flox/flox mice. Results: PTEN invalidation alleviates experimental colitis induced by DSS, as evidenced by decreased weight loss during the acute phase, the lower expression of inflammation markers, including the proinflammatory cytokines IFN-γ, CXCL1 and CXCL2, reduced mucosal lesions, and faster recovery after resolution of inflammation. This protective effect might result in part from the sustained proliferation of colonic epithelium, leading to hyperplasia and increased colonic crypt depth under physiological conditions, which was further exacerbated in the vicinity of mucosal injury induced by DSS treatment. Furthermore, PTEN knockout decreased paracellular permeability, thereby enhancing the intestinal barrier function. This process was associated with the reinforcement of claudin-3 immunostaining, especially on the surface epithelium of villin-Cre PTEN^flox/flox mice. Conclusions: PTEN inactivation exerts a protective effect on the onset of colitis, and the transient and local down-modulation of PTEN might constitute an approach to drive recovery following acute intestinal inflammation. Full article

Some pancreatic ductal-type (PDADK) and lung adenocarcinomas (LADK) lacking other molecular drivers are reported to harbor NRG1 fusions as potential novel therapeutic targets. We investigated the feasibility of a fluorescent in situ hybridization (FISH)-based diagnosis of NRG1 fusions in a case series of PDADK and LADK lacking other identified oncogenic drivers. First, among a case series of PDADK, KRAS analyses (PCR followed in PCR-negative cases by RNA sequencing—RNAseq) found 27/162 (16.7%) KRAS wild-type cases, among which 1/162 (0.6%) NRG1 fusion was diagnosed using FISH. Secondly, among a case series of LDAK, 191/446 (42.8%) cases had no molecular alterations in EGFR, KRAS, BRAF, HER2, MET, ALK, ROS1 and RET according to NGS and FISH analyses and, among them, 4/446 (0.9%) cases had NRG1 fusions using FISH. Finally, four additional cases out of the two previously mentioned cases series (1 PDADK and 3 LADK) with NRG1 fusions diagnosed by first-line RNAseq were also concluded as NRG1 FISH-positive. The NRG1 FISH tests for the nine NRG1 FISH-positive cases resulted in 50% to 80% of positive tumor nuclei, all with single 3′-NRG1 FISH signals. In our series, of the 22 cases analyzed with both NRG1 FISH (positivity criterion of at least 15% of tumor nuclei with a split between the 5′- and the 3′- parts of the probes and/or isolated single 3′-NRG1 signal) and RNAseq, 17 cases were FISH– RNAseq– and 5 cases were FISH+ RNAseq+ (no FISH+ RNAseq– or FISH– RNAseq+ cases in our study) resulting in 100% sensibility and specificity for the NRG1 FISH test. In the case of no access to RNAseq, NRG1 FISH consists of a valuable tool searching for NRG1 fusions in patients with advanced cancers. Full article

Background/Objectives: Response to immune checkpoint inhibitors (ICIs) is associated with several biological pathways, including tumor immunogenicity and antitumor immunity. Identifying host factors involved in these pathways may guide personalized ICI treatment. Methods: We describe the application of chromatin conformation assays to blood from patients with advanced urothelial carcinoma from the phase 3 JAVELIN Bladder 100 trial (NCT02603432). This trial demonstrated a significant survival benefit with avelumab maintenance plus best supportive care (BSC) vs. BSC alone following non-progression with platinum-based chemotherapy as first-line therapy. Blood-based chromatin conformation markers (CCMs) were screened for associations with high/low immune effector gene expression in tumors and for interactions with outcomes and tumor mutation burden. Results: Candidate CCMs included genes involved in several immune response pathways, such as POU2F2, which encodes a transcription factor that regulates B-cell maturation. Conclusions: Our findings suggest that polygenic host factors may affect response to ICIs and support further investigation of chromatin conformation assays. Full article

Background: Texture analysis (TA) has shown promise in characterizing intratumoral heterogeneity from imaging data. We add to the literature that shows its capability to differentiate oropharyngeal cancers based on HPV status. Methods: Multislice CT analysis was done in 120 patients with confirmed OP SCC: a single 5 mm region of interest was placed on three consecutive homogeneous CT slices per patient. Texture features were extracted by using gray-level co-occurrence matrices averaged per patient. HPV status (via p16 IHC and molecular confirmation) and differentiation grade (i.e., good, moderate, and poor) were recorded. Non-parametric statistical tests assessed differences between subgroups. Results: Seven texture parameters (i.e., angular second moment, contrast, sum of squares, sum entropy, entropy, inverse difference moment, and difference variance) differed significantly between HPV+ and HPV− tumors (all p < 0.05). HPV+ tumors exhibited increased heterogeneity and complexity on CT imaging. No texture feature correlated with histological grade. Conclusions: This study adds to the growing evidence that CT-based TA can assess HPV status in OP SCC. TA may be promising, though it requires further validation as an adjunctive method integrating into radiomics workflows to develop predictive models for diagnosis, prognosis, and treatment planning. Full article

Background/Objectives: Circulating tumor cells (CTCs) are important biomarkers for predicting prognosis and evaluating treatment efficacy in cancer. We developed the “CTC-Chip” system based on microfluidics, enabling highly sensitive CTC detection and prognostic assessment in lung cancer and malignant pleural mesothelioma. However, the final identification and enumeration of CTCs require manual intervention, which is time-consuming, prone to human error, and necessitates the involvement of experienced medical professionals. Medical image recognition using machine learning can reduce workload and improve automation. However, CTCs are rare in clinical samples, limiting the training data available to construct a robust CTC image recognition system. In this study, we established a highly accurate artificial intelligence-based CTC recognition system by pre-training convolutional neural networks using images from lung cancer cell lines. Methods: We performed transfer learning of convolutional neural networks. Initially, the models were pre-trained using images obtained from lung cancer cell lines. The model’s accuracy was improved by training with a limited number of clinical CTC images. Results: Transfer learning significantly improved the CTC classification accuracy to an average of 99.51%, compared to 96.96% for a model trained solely on pre-trained cell lines (p < 0.05). This approach showed notable efficacy when clinical training images were limited, achieving statistically significant accuracy improvements with as few as 17 clinical CTC images (p < 0.05). Conclusions: Overall, our findings demonstrate that pre-training with cancer cell lines enables rapid and highly accurate automated CTC recognition even with limited clinical data, significantly enhancing clinical applicability and potential utility across diverse cancer diagnostic workflows. Full article

Head and neck squamous cell carcinomas (HNSCCs) that develop from the mucosal epithelium in the oral cavity, pharynx, and larynx are a heterogeneous group of malignant tumors. A lack of appropriate screening and diagnostic methods leads to late diagnoses, with the majority of patients having locally advanced disease, which is associated with a high risk of local recurrence and a poor prognosis and is usually treated with combination therapies. Biomarkers for predicting the therapy response and risk of recurrence in HNSCC patients are urgently needed. Liquid biopsy, e.g., the profiling of circulating biomarkers in bodily fluids, is a promising approach with increasing utility in the early detection and diagnosis of cancer, monitoring cancer progression, patient stratification and treatment selection, detecting minimal residual disease (MRD), and predicting recurrence across different cancer types, including HNSCC. Among liquid biomarkers, circulating tumor DNA (ctDNA), which is based on detecting tumor-specific mutations, insertions/deletions, copy number alterations, and methylation, is the most promising transformative tool in cancer management and personalized cancer treatment. In this review, we provide an update of recent data on the role of non-viral ctDNA in the management of HNSCC patients. Accumulating data suggests the enormous potential of ctDNA profiling by serial sampling during and after definitive therapy in detecting MRD and predicting recurrence in HNSSC patients treated with a single treatment modality (surgery or radiotherapy) or with combination therapies, including immune-checkpoint-inhibitor-based immunotherapy. By incorporating the latest immunotherapy trials and organizing the data by the treatment modality, this review offers a novel perspective not found in previous surveys. Full article

Background/Objectives: The neurotrophic tropomyosin receptor kinase (NTRK) genes NTRK1, NTRK2, and NTRK3 encode tyrosine kinase receptors, and their fusion genes are known as the oncogenic driver genes for cancer. This study aimed to compare the diagnostic ability of NTRK fusion among five types of multi-cancer genome profiling tests (multi-CGP tests) and determine a useful multi-CGP test for NTRK fusion, recorded in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. This study aimed to compare the diagnostic results for NTRK fusions among the five different CGP tests. Methods: A total of 88,688 tumor cases were enrolled in the C-CAT profiling database from 2019 to 2024. The detection frequency of NTRK fusion genes was compared to the results for five multi-CGP tests: NCC Oncopanel, FoundationOne CDx (F1), FoundationOne Liquid (F1L), GenMineTOP (GMT), and Guardant360. Results: NTRK fusion genes were detected in 175 (0.20%) of the 88,688 total cases. GMT, which is equipped with RNA sequencing function, frequently detected NTRK fusion genes (20 of 2926 cases; 0.68%) in comparison with the other four multi-CGP tests that do not have RNA sequencing analysis. GMT showed significantly (p < 0.05) higher diagnostic ability for NTRK fusions compared with the other four multi-CGP tests. Especially, NTRK2 fusion was significantly (p < 0.001) more highly determined by GMT than it was by the other four multi-CGP tests. The detection rates for FGFR1 and FGFR3 were significantly higher in GMT than in other multi-CGP tests. In contrast, the detection rates of the ALK and RET fusion genes were significantly higher in F1L. Conclusions: GMT, which is equipped with RNA sequencing analysis, might show a useful diagnostic ability for NTRK fusions, especially for NTRK2 fusion genes. Full article