Search Results (806)

Background: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy arising from the nasopharyngeal mucosa. Despite treatment advances such as the use of intensity-modulated radiotherapy and immune checkpoint inhibitors, resistance remains a significant clinical challenge. Many tumours are also diagnosed at an advanced stage associated with poor prognosis. Objective: This review aims to explore the biological roles of autophagy in NPC, primarily highlighting its involvement in disease pathogenesis and treatment resistance. Methods: We performed a review of the recent literature examining the role of autophagy-related pathways in NPC pathogenesis, biomarker discovery, and therapeutic targeting. Results: Autophagy plays a dual role in NPC as it contributes to both tumour suppression and progression. It is involved in tumour initiation, metastasis, immune modulation, and treatment resistance. Autophagy-related genes such as SQSTM1, Beclin-1, and AURKA may serve as prognostic and therapeutic biomarkers. Various strategies are being investigated for their role to modulate autophagy using pharmacologic inhibitors, RNA interventions, and natural compounds. Conclusions: Further research into autophagy’s context-dependent roles in NPC may inform the development of personalised therapies and allow progress in translational and precision oncology. Full article

Bladder cancer pathogenesis is closely linked to epigenetic alterations, particularly DNA methylation and demethylation processes. Environmental carcinogens and persistent inflammatory stimuli—such as recurrent urinary tract infections—can induce aberrant DNA methylation, altering gene expression profiles and contributing to malignant transformation. This review synthesizes current evidence on the role of DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) and the hypermethylation of key tumour suppressor genes, including A2BP1, NPTX2, SOX11, PENK, NKX6-2, DBC1, MYO3A, and CA10, in bladder cancer. It also evaluates the therapeutic application of DNA-demethylating agents such as 5-azacytidine and highlights the impact of chronic inflammation on epigenetic regulation. Promoter hypermethylation of tumour suppressor genes leads to transcriptional silencing and unchecked cell proliferation. Urine-based DNA methylation assays provide a sensitive and specific method for non-invasive early detection, with single-target approaches offering high diagnostic precision. Animal models are increasingly employed to validate these findings, allowing the study of methylation dynamics and gene–environment interactions in vivo. DNA methylation represents a key epigenetic mechanism in bladder cancer, with significant diagnostic, prognostic, and therapeutic implications. Integration of human and experimental data supports the use of methylation-based biomarkers for early detection and targeted treatment, paving the way for personalized approaches in bladder cancer management. Full article

Docetaxel is a chemotherapeutic agent widely used for breast cancer treatment; however, its efficacy is often limited by drug resistance and associated toxicity. This review examines the molecular mechanisms of docetaxel resistance in breast cancer and discusses research advances and future directions for overcoming this challenge. Key resistance mechanisms include alterations in drug targets (microtubules), increased drug efflux, suppression of apoptosis, activation of survival signalling pathways, epithelial-to-mesenchymal transition (EMT), and cancer stem cell enrichment. An evolutionary perspective distinguishes between intrinsic and acquired resistance, emphasising the need for adaptive therapeutic strategies. Recent advances in genomic profiling, non-coding RNA research, novel drug combinations, and biomarker-guided therapies have also been reviewed. Emerging approaches, such as targeting the tumour microenvironment, harnessing immunotherapy, and implementing adaptive dosing schedules, have been discussed. This review emphasises the understanding of resistance as a multifactorial phenomenon that requires multipronged interventions. Research has aimed to identify predictive biomarkers, develop targeted agents to reverse resistance, and design rational combination strategies to improve patient outcomes. Progress in deciphering and targeting docetaxel resistance mechanisms holds promise for enhancing treatment responses and extending survival in patients with breast cancer. Full article

Background/Objective: One third of “non-functioning adrenal tumours” (NFAs) have mild autonomous cortisol secretion (MACS). An updated analysis of the hormonal biomarkers profile, including risk factors and the rate of post-surgery adrenal insufficiency (PSAI), the duration of restoring the normal adrenocortical function in MACS/NFA and potential impacts on clinical comorbidities. Methods: Comprehensive review based on PubMed search (January 2020–January 2025). Results: The studies (n = 14) included 2623 patients (N = 1158 underwent unilateral adrenalectomy), aged 18–93 (mean = 57.49 years), with a female-to-male ratio = 1.54. Post-adrenalectomy (n = 9, N = 753) analysis: the PSAI risk correlated with the severity of baseline hypercortisolism. PSAI incidence: 50% of MAC. The rate after 4–6 weeks follow-up was 71.9% (adrenal Cushing’s syndrome) vs. 50% (MACS) vs. 14.4% (NFA). PSAI duration was up to 35 months. Early PSAI diagnosis was reflected by post-operative cortisol assay on day 1 (cut-off ≤ 5 µg/dL) and an ACTH (Cosyntropin) stimulation test (CST) (cortisol cut-off ≤ 14 µg/dL). Pre-operatory PSAI predictors: higher serum cortisol-DST (1 mg dexamethasone testing) and lower baseline plasma ACTH (not all studies agreed). Conclusions: A stratified strategy is encouraged following a unilateral adrenalectomy in MACS; PSAI is expected in almost half of patients, with a potential improvement of hypertension. Serum cortisol assays serve as most useful biomarker as pre-operatory PSAI predictor (after DST) and, potentially, in addition with baseline ACTH. Post-surgery basal cortisol measurement (± CST) helps the decision of glucocorticoids replacement since first post-operative day and during follow-up, serial testing at 3 months is a useful tool. Full article

Background: The accurate prediction of pathological complete response (pCR) following total neoadjuvant therapy (TNT) is crucial for optimising treatment protocols in locally advanced rectal cancer (LARC). Although conventional imaging techniques such as MRI show limitations in assessing treatment response, metabolic imaging utilising 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) provides distinctive information by quantifying tumour glycolytic activity. This study investigates the predictive value of sequential 18F-FDG PET-CT parameters, focusing on Total Lesion Glycolysis (TLG), in predicting pCR after TNT. Methods: We conducted a retrospective analysis of 33 LARC patients (T3–4/N0–1) treated with TNT (neoadjuvant-chemoradiation followed by consolidation FOLFOX chemotherapy). Sequential PET-CT scans were performed at baseline, interim (after 4 cycles of FOLFOX), and post-TNT. Metabolic parameters, including maximum standardised uptake value (SUVmax) and TLG, were measured. Receiver operating characteristic (ROC) analysis assessed the predictive performance of these parameters for pCR. Results: The pCR rate was 21.2% (7/33). Post-TNT TLG ≤ 10 demonstrated excellent predictive accuracy for pCR (AUC 0.887, 92.3% sensitivity, 85.7% specificity, and 96.0% PPV), outperforming SUVmax (AUC 0.843). Interim TLG ≤ 10 also showed a strong predictive value (AUC 0.824, 100% sensitivity, and 71.4% specificity). Conclusions: TLG may serve as a reliable metabolic biomarker for predicting pathologic complete response (pCR) after total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC). Its inclusion in clinical decision-making could improve patient selection for organ preservation strategies, thereby reducing the need for unnecessary surgeries in the future. However, given that the study is based on a small retrospective design, the findings should be interpreted with caution and used alongside other decision-making tools until more comprehensive data are collected from larger studies. Full article

Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive subtype of non-Hodgkin lymphoma, the monitoring of which is largely restricted to radiological methods. Diagnosis relies on identifying characteristic clinicopathological features, supported by the detection of recurrent somatic mutations in RHOA, TET2, IDH2 and DNMT3A. The characteristic molecular profile of AITL and the high levels of circulating tumour DNA (ctDNA) measurable in AITL before treatment makes this an attractive lymphoma subtype in which to further investigate the role of ctDNA monitoring. The detection of somatic mutations in pre-treatment AITL-containing tissue samples was compared to those detected in pre-treatment ctDNA samples in a cohort of 12 patients. Changes in ctDNA somatic mutation burden over time were then correlated with radiological response. All six paired pre-treatment ctDNA and tissue samples had variants in common. All (8/8) previously ctDNA-detectable IDH2 and RHOA variants were undetectable in ctDNA samples at the time of end-of-treatment complete metabolic response (CMR). In comparison, the majority of both previously ctDNA-detectable DNMT3A variants (3/4) and TET2 variants (6/11) were detectable in ctDNA samples at the time of end-of-treatment CMR. These observations suggest that IDH2/RHOA variants may be more reliable markers of measurable residual disease in AITL than DNMT3A/TET2 variants. Full article

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, but its molecular drivers remain underexplored in Latin American populations. This study investigated the prevalence, co-occurrence, and tissue distribution of somatic mutations in the TERT promoter (C228T/C250T) and CTNNB1 exon 3, as well as TERT gene expression, in liver tissues from Brazilian patients. A total of 85 samples (42 HCC, 21 cirrhosis, and 22 hepatitis) were analysed using Sanger sequencing and RT-qPCR. TERT promoter mutations were detected in 47.6% of HCC tissues, including C228T (45.2%) and C250T (2.4%), and were also present in 19% of cirrhotic tissues but absent in hepatitis samples, supporting their emergence in early hepatocarcinogenesis. CTNNB1 exon 3 mutations occurred in 17.2% of HCCs and significantly co-occurred with TERTp mutations (66.7%, p = 0.0485), although the number of CTNNB1-mutated cases was limited. TERT expression was significantly upregulated in HCC tissues regardless of mutation status (p < 0.001). This is the first study to characterise these mutations in Brazilian HCC patients, highlighting the C228T mutation as a promising biomarker for early detection and molecular surveillance in cirrhotic individuals. Despite the genetic admixture of the studied population, the mutational patterns were comparable to those reported in more homogeneous populations, reinforcing the global relevance of these molecular alterations. Full article

Although immunotherapy has led to a breakthrough in the treatment of NSCLC, fast disease progression in some patients remains problematic. Great efforts are being made to identify the mechanisms of immune resistance and to establish new predictive and prognostic biomarkers. The aim of this study was to evaluate the association between PD-L1 expression, genetic alterations, and prognosis in patients diagnosed with metastatic NSCLC. PD-L1 expression and genetic profiling using NGS were assessed in 50 patients with advanced NSCLC who were negative for EGFR mutations. According to this study results, positive PD-L1 expression was detected in 62% of cases, whereas high TMB was detected in 34% of cases. Targetable mutations were detected in 33.4% of cases. The TP53 mutation was more likely to be found in tumours with higher PD-L1 and TMB levels (median 45 vs. 0, p = 0.005; median 10 vs. 4.5, p = 0.008, respectively). Meanwhile, STK11 mutation was associated with lower PD-L1 and higher TMB levels (median 0 vs. 17.5, p = 0.019; median 11.5 vs. 6, p = 0.047). Fast disease progression was observed in 22.2% of cases when immunotherapy alone or combined with chemotherapy was administered, with the most frequently detected TP53 (87.5%), STK11 (37.5%), and KEAP1 (37.5%) mutations in this part of the population. Progressive disease was more likely to be found in patients with KEAP1 mutation than in those with wild-type KEAP1 (75% vs. 18.8%, p = 0.02). To conclude, significant associations were found between PD-L1, TMB statuses and mutations in STK11 and TP53. Fast disease progression was established in 1/5 of the entire population treated with immunotherapy or chemo-immunotherapy. TP53, STK11, and KEAP1 mutations were most frequently detected in patients with fast disease progression. The KEAP1 mutation was associated with progressive disease in patients with advanced NSCLC. Our results suggest that a specific genetic profile could serve as a predictor of fast progression in a selected group of patients. Full article

The interaction of programmed cell death receptor 1 (PD-1) on the surface of immune cells with its ligand, programmed cell death ligand 1 (PD-L1), expressed on tumour cells and antigen-presenting cells, leads to tumour immune evasion. Antibodies that target either PD-1 or its ligand PD-L1 have shown a favourable response in cancer patients, especially those with non-small cell lung cancer (NSCLC). However, only 15 to 25% of advanced NSCLC patients will benefit from immunotherapy. The PD-L1 tumour proportion score (TPS) is the current standard biomarker to select patients for PD-1/PD-L1 blockade therapy, as patients with a high PD-L1 TPS show better response compared to patients with a low PD-L1 TPS. However, since PD-L1 expression is a continuous variable and is an imperfect biomarker, investigation into additional predictive markers is warranted. This review focuses on tumour- and non-tumour-associated factors that have been shown to affect the response to PD-1/PD-L1 inhibitors in NSCLC. We also delve into mechanistic and clinical evidence on these potential biomarkers and their relationship to the tumour microenvironment (TME). Full article

Cancer metabolism is a hallmark of cancer. However, the impact of systemic metabolism and diet on tumour evolution is less understood. This study delves into the role of glucagon, as a component of the pancreatic microenvironment, in regulating features of pancreatic neuroendocrine tumour (pNET) cells and the metabolic remodelling occurring in the presence and absence of glucose. pNET cell lines (BON-1 and QGP-1) and the non-malignant pancreatic α-TC1 cell line were used as models. Results showed that pNET cells responded differently to glucose deprivation than α-TC1 cells. Specifically, pNET cells upregulated the GCGR in the absence of glucose, while α-TC1 cells did so in high-glucose conditions, allowing the glucagon-related pERK1/2 activation under these conditions in pNET cells. Glucagon enhanced cancerous features in pNET BON-1 cells under glucose-deprived and hyperglucagonemia-compatible concentrations. In the α-TC1 cell line, glucagon modulated cell features under high-glucose and physiological glucagon levels. NMR exometabolome analysis revealed differences in metabolic processes based on glucose availability and glucagon stimulation across cell lines, highlighting amino acid metabolism, glycolysis, and gluconeogenesis. The expression of metabolic genes was consistent with these findings. Interestingly, QGP-1 and α-TC1 cells produced glucose in no-glucose conditions, and glucagon upregulated glucose production in α-TC1 cells. This suggests that gluconeogenesis may be beneficial for some pNET subsets, pointing out novel metabolism-based strategies to manage pNETs, as well as a step forward in endocrinology and systemic metabolism. The association between GCGR expression and malignancy and a negative correlation between glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) expression was observed, indicating a biological role of glucagon in pNETs that deserves to be explored. Full article

Despite numerous studies, colon cancer is still one of the leading cancers in the world, both in terms of incidence and mortality. One of the most important methods of monitoring and studying changes in cancer is the use of biomarkers in the form of microRNA. Their remarkable stability and detectability in body fluids make them promising diagnostic and prognostic biomarkers. This review highlights selected deregulated miRNAs in colorectal cancer, including miR-21, miR-29b, miR-148a, miR-149, miR-155, miR-194, and miR-200b and lesser known ones such as miR-6803-5p or miR-4772-3p. Deregulation of their expression in colon cancer is associated with abnormal cell proliferation, migration, changes in the microenvironment or response to treatment, caused by their involvement in such pathways as Wnt/β-catenin, PI3K/Akt or EGFR. Additionally, we explore their therapeutic potential, particularly their ability to enhance tumour sensitivity to chemotherapeutic agents like 5-FU and oxaliplatin. The purpose of this review is to emphasize the growing relevance of miRNAs as both non-invasive diagnostic tools and potential therapeutic targets in colorectal cancer management. Full article

This review highlights recent findings on the versatile serpin protein, pigment epithelium-derived factor (PEDF), in relation to cancer diagnosis, treatment and prognosis. PEDF was initially discovered in the eye but has since been reported to be relevant to various biological roles in the body, and when awry, to clinically lead to various disease states such as neoplasia. At the preclinical stage, potent effects have been reported in studies focussing on apoptosis, metastasis, oxidative stress, immune stimulation and metabolism. Apart from full-length proteins, short peptides based on PEDF have shown promise against cancer. For diagnosis and prognosis, PEDF levels in tumour specimens or in circulation have the potential to serve as biomarkers, most probably in combination with other biomarkers of cancer initiation and progression. Lastly, this review discusses the growing list of studies that point out the perceived pro-cancerous effects of PEDF, though this is clearly outweighed by the anticancer publications. Thus, this review provides a comprehensive and balanced listing of the oncological studies associated with this protein to date, drawing conclusions on whether this potent antiangiogenic protein and its peptides can be used in the future for better cancer treatment, especially against metastasis. Full article

Temporomandibular disorders (TMDs) impact quality of life and present diagnostic and treatment challenges. Biomarkers may serve as an additional tool to support diagnosis and monitor disease progression, offering supplementary information for treatment strategies in specific and selected patients. This systematic review aimed to assess the role of biomarkers in diagnosing TMD and guiding personalized treatment. It also examined key biomarkers linked to chronic temporomandibular joint (TMJ) pain and how therapies affect biomarker levels and clinical outcomes. A comprehensive search was conducted in PubMed, Scopus, and Web of Science to identify observational and interventional studies assessing the role of biomarkers in synovial fluid/tissue, saliva, and blood. The research was registered in PROSPERO, adhered to PRISMA guidelines, and employed Cochrane Risk of Bias tools. To assess the effect, only studies examining biomarker levels were considered. A total of forty-six studies met the inclusion criteria: three randomized controlled trials were rated as having some concerns, as were most of the observational studies. Elevated levels of interleukins (1ß and 6), tumour necrosis factor alpha, and prostaglandin E2 in synovial fluid were correlated with temporomandibular joint (TMJ) inflammation. Increased matrix metalloproteinases (2, 7, and 9) indicated cartilage deterioration, while oxidative stress markers such as malondialdehyde were higher in TMD patients. Treatments including hyaluronic acid, platelet-rich plasma, and low-level laser therapy effectively reduced inflammatory biomarkers and improved symptoms. Biomarkers show potential to contribute to the understanding of pathophysiological mechanisms in TMD and may support future diagnostic and therapeutic strategies for selected patients. After high-quality studies confirm these findings, this approach will enable personalized medicine by tailoring treatments to individual patient profiles, ultimately leading to improved outcomes and quality of life. Full article

Circulating tumour DNA (ctDNA) is a promising biomarker for personalised oncology. However, its clinical utility is limited by detection sensitivity, particularly in early-stage disease. T-Oligo Primed Polymerase Chain Reaction (TOP-PCR) is a commercial amplification approach utilising an efficient “half-adapter” ligation design and a single-primer-based PCR strategy. This study evaluated the clinical value and application of cell-free DNA (cfDNA) pre-amplification. cfDNA amplification with TOP-PCR preserved DNA size profiles and resulted in a 22 bp size increase due to the half-adaptor ligation. Gene target amplification rates varied, showing lower efficiency for the GC-rich TERT promoter amplicon and higher efficiency for the BRAF and TP53 amplicons. Optimised pre-amplification (20 ng cfDNA input and 5–7 cycles of PCR) enhanced ctDNA detection sensitivity and expanded sample availability for the detection of multiple tumour-informed mutations. Importantly, PCR errors emerged in pre-amplified cfDNA samples, underscoring the necessity for negative controls and the establishment of stringent mutation positivity thresholds. Full article

The aberrant DNA methylation of tumour suppressor genes, including CADM1, MAL, and PAX1, is implicated in cervical carcinogenesis. Objectives: This pilot study aimed to evaluate the methylation levels of these genes in HPV-positive women and assess their diagnostic performance for detecting histologic high-grade squamous intraepithelial lesions (HSILs) and carcinoma. Methods: Cervical samples from 73 HPV-positive women were analyzed using droplet digital PCR (ddPCR) to quantify methylation levels of CADM1, MAL, and PAX1. The methylation levels were further compared across cytological and histological classifications. A control group of 26 HPV-negative women with negative cytology was also included. The diagnostic performance was assessed through receiver operating characteristic (ROC) analysis, as well as sensitivity and specificity calculations for individual genes and gene panels. Results: MAL methylation was absent in NILM, LSIL, and HSIL samples but was significantly elevated in carcinoma. PAX1 methylation was observed in both high-grade and some low-grade lesions. CADM1 methylation remained low or undetectable in the NILM, LSIL, and HSIL groups, with a significant increase observed in carcinoma cases. The CADM1/MAL panel demonstrated the highest diagnostic accuracy, with an area under the curve (AUC) of 0.912, 70% sensitivity, and 100% specificity. ddPCR exhibited superior analytical sensitivity compared to real-time PCR. Conclusions: The CADM1/MAL methylation panel, assessed by ddPCR, may serve as a specific biomarker for the triage of HPV-positive women at risk of HSIL and carcinoma. However, this study’s limited sample size and single-centre design necessitate cautious interpretation. Further validation in larger, population-based cohorts is necessary to confirm its clinical utility. Full article