Aggressive Features Research Articles

WD repeat domain 4 in tumorigenesis: Molecular mechanisms, cancer-type specific roles, and therapeutic potential

WD repeat domain 4 (WDR4) is an essential member of the WD-repeat protein family, known for its regulatory roles in cellular processes critical to cancer development, including RNA modification, protein stability, cell cycle progression, and apoptosis. Studies have shown that WDR4 plays a pivotal role in tumorigenesis across various cancer types, with a particular focus on breast cancer in this study, where its overexpression is closely associated with aggressive tumor characteristics and poorer patient outcomes. As a scaffold protein, WDR4 is involved in N7-methylguanosine tRNA methylation and ubiquitin-mediated protein degradation, thereby regulating RNA stability, protein synthesis, and cell survival. This review provides a comprehensive analysis of WDR4’s molecular mechanisms, its oncogenic functions across different cancer types, and its interactions with other key factors in the tumor microenvironment, further exploring its potential role in tumor progression. As research on WDR4 progresses, we not only gain a deeper understanding of its complex role in tumor biology but also uncover new therapeutic avenues. In particular, the potential of WDR4 as a biomarker and therapeutic target is increasingly recognized. Despite the challenges faced in its clinical application, such as the difficulty in developing targeted therapies and managing side effects, the future prospects of WDR4 in cancer diagnosis and treatment remain promising, and it is expected to emerge as an effective therapeutic target in the near future.

Association between muscle mass, visceral adiposity, and histologic tumor stromal features in colon cancer.

Sarcopenia and obesity are indicators for poor outcomes in colon cancer. Additionally, aggressive histopathologic tumor stromal features, such as a low tumor-stroma ratio (TSR) and low tumor-infiltrating lymphocytes (TILs) predict survival and treatment response. As their relationship remains underexplored, we studied the association between skeletal muscle mass, visceral adipose tissue (VAT), TSR, and TILs in patients with colon cancer. We studied 194 stage II/III colon carcinoma patients who underwent elective surgery. Preoperative computed tomography (CT) scans classified patients into four groups based on skeletal muscle index (normal/low) and visceral adipose tissue index (normal/high). Tumor tissues were assessed for TSR and TILs, and five-year disease recurrence and relative hazard were evaluated. Among the patients, 56 (28.9%) were classified as Normal Muscle, Normal VAT, 26 (13.4%) as Normal Muscle, High VAT, 75 (38.7%) as Low Muscle, Normal VAT, and 37 (19.1%) as Low Muscle, High VAT. Patients with low skeletal muscle mass were more often male (62.5% vs. 39%, P=0.005). Stroma-high tumors were less common in Low Muscle, Normal VAT patients (24%) compared to Normal Muscle, High VAT (50%), Low Muscle, High VAT (48.6%), and Normal Muscle, Normal VAT (41.1%) patients (P=0.020). Tumors with low TILs were similarly distributed across groups (P=0.679). Low Muscle, Normal VAT patients had a lower recurrence hazard compared to both Low Muscle, High VAT (hazard ratio [HR] 0.34, 95% CI 0.12-0.98, P=0.048) and Normal Muscle, Normal VAT (HR 0.31, 95% CI 0.11-0.87, P=0.027) patients. Low Muscle, Normal VAT colon cancer patients exhibited fewer aggressive tumor features and a lower recurrence risk compared to Low Muscle, High VAT patients. These findings highlight the importance of body composition in tumor biology and prognosis.

Isolated Tuberculoma Involving Multiple Paranasal Sinuses with Aggressive Features in an Immunocompetent Individual Masquerading as a Malignant Neoplasm: A Rarity Unveiled with Review of Literature

Isolated Tuberculoma Involving Multiple Paranasal Sinuses with Aggressive Features in an Immunocompetent Individual Masquerading as a Malignant Neoplasm: A Rarity Unveiled with Review of Literature

Multilevel plasticity and altered glycosylation drive aggressiveness in hypoxic and glucose-deprived bladder cancer cells.

Bladder tumors with aggressive characteristics often present microenvironmental niches marked by low oxygen levels (hypoxia) and limited glucose supply due to inadequate vascularization. The molecular mechanisms facilitating cellular adaptation to these stimuli remain largely elusive. Employing a multi-omics approach, we discovered that hypoxic and glucose-deprived cancer cells enter a quiescent state supported by mitophagy, fatty acid β-oxidation, and amino acid catabolism, concurrently enhancing their invasive capabilities. Reoxygenation and glucose restoration efficiently reversed cell quiescence without affecting cellular viability, highlighting significant molecular plasticity in adapting to microenvironmental challenges. Furthermore, cancer cells exhibited substantial perturbation of protein O-glycosylation, leading to simplified glycophenotypes with shorter glycosidic chains. Exploiting glycoengineered cell models, we established that immature glycosylation contributes to reduced cell proliferation and increased invasion. Our findings collectively indicate that hypoxia and glucose deprivation trigger cancer aggressiveness, reflecting an adaptive escape mechanism underpinned by altered metabolism and protein glycosylation, providing grounds for clinical intervention.

Molecular and pathological landscape of the AT-rich interaction domain 1A (ARID1A) mutation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with complex etiological factors and a diverse genetic landscape. Among the critical genetic mutations in HCC, the AT-rich interaction domain 1 A (ARID1A) gene, a key component of the SWI/SNF chromatin remodeling complex, stands out due to its significant role in both tumor suppression and oncogenesis. This review comprehensively examines the molecular and pathological impacts of ARID1A mutations in HCC. ARID1A mutations, which occur in approximately 7.9 % of HCC cases, predominantly involve truncating mutations leading to loss of function. These mutations are associated with various aggressive cancer features, including larger tumor size, higher rates of metastasis, and poor prognosis. The dual role of ARID1A in HCC is context-dependent, acting as a tumor suppressor by regulating cell cycle control, DNA damage repair, and gene expression, while also displaying oncogenic properties in specific contexts by promoting early tumorigenesis through oxidative stress pathways. Understanding the molecular mechanisms of ARID1A, including its interactions with key cellular pathways such as PI3K/AKT/mTOR, β-catenin, and PD-L1, provides insights into its complex role in HCC pathogenesis. Furthermore, ARID1A's impact on cancer stem cell maintenance, metabolic reprogramming, and immune evasion underscores its potential as a therapeutic target. This review highlights the need for context-specific therapeutic strategies targeting ARID1A, which could lead to more effective treatments for HCC, addressing both its tumor-suppressive and oncogenic activities.

False-Negative Review from the Mammography Audit: Refining Breast Imaging Practice.

Annual review of false-negative (FN) mammograms is a mandatory and critical component of the Mammography Quality Standards Act (MQSA) annual mammography audit. FN review can help hone reading skills and improve the ability to detect cancers at mammography. Subtle architectural distortion, asymmetries (seen only on one view), small lesions, lesions with probably benign appearance (circumscribed regular borders), isolated microcalcifications, and skin thickening are the most common mammographic findings when the malignancy is visible at retrospective review of FN mammograms. Most FN mammograms are not due to radiologist error. There are common and predictable settings in which FN mammograms occur. Patient factors associated with elevated FN mammograms include dense breasts, elevated lifetime risk of breast cancer, and personal history of breast cancer treated with lumpectomy and radiation therapy. About half of FN cancers are detected by supplemental screening examinations and half manifest clinically. The most common manifesting symptoms for interval cancers are a palpable abnormality, nipple discharge, and skin changes. Interval cancers can have more aggressive pathologic features and higher rates of node positivity. The FN review includes Breast Imaging Reporting and Data System (BI-RADS) 3 cases that develop a cancer diagnosis during surveillance. Nonbreast malignancies diagnosed as interval cancers (most commonly lymphoma and metastatic disease) do not need to be counted as FNs for audit purposes. The FN review and annual audit are confidential processes that protect patient and radiologist information while allowing meaningful quality control and improvement. Although FN mammograms are rare, review of these cases is a valuable educational tool. The slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2025.

In Search of Representative Translational Cancer Model Systems.

Racial disparities in cancer outcomes are well documented across tumor types. For patients with breast cancer, Black women are more likely to present with more aggressive molecular features and more likely to die from disease, even after accounting for those features. Recent efforts have been aimed at developing translational model systems for precision medicine strategies, and a major focus has been on patient-derived organoids. Organoids allow for robust in vitro experimental platforms, including drug and CRISPR screens while maintaining more complex cancer and tumor microenvironment subpopulations than cell lines. For results that are broadly translationally relevant, it is important that cancer models are derived from the spectrum of human disease and humans with disease. In this issue of Cancer Research, Madorsky Rowdo and colleagues derive breast cancer organoids from patients with African ancestry and use CRISPR-Cas9 screens to identify novel therapeutic vulnerabilities. These findings demonstrate the promise of representative cancer model systems to facilitate discoveries that are most likely to translate to improved therapy for all patients. See related article by Madorsky Rowdo et al., p. 551.

Association of GPR120 and NGF with perineural invasion in cholangiocarcinoma: Clinical and experimental insights.

622 Background: Cholangiocarcinoma (CCA) is a highly malignant biliary tumor characterized by frequent perineural invasion (PNI), which is associated with a poor prognosis; however, the underlying mechanisms remain unclear. G-protein-coupled receptor 120 (GPR120) has been implicated in the development of various tumors, while nerve growth factor (NGF) has a strong correlation with PNI. This study aims to elucidate the role of GPR120 in the production of NGF and to investigate the mechanisms by which PNI is induced in CCA. Methods: We conducted a retrospective review of medical records for 386 patients with cholangiocarcinoma (CCA), including both extrahepatic (ECC) and intrahepatic (ICC) types, who underwent curative resection at the Department of General Surgery, First Affiliated Hospital of Soochow University, between January 2015 and December 2021. NGF and GPR120 expression were assessed in 60 paraffin-embedded archived CCA tissue samples via immunohistochemical staining (IHC), with an additional 60 normal bile duct samples serving as controls. All tissues were sourced from the aforementioned 386 patients, none of whom received preoperative treatment. Tumors were staged according to AJCC classification. Western blot analysis was employed to evaluate NGF and GPR120 expression in CCA cell lines (QBC 939, RBE, HUCCT-1, and HCCC-9810). To assess the invasion and migration capabilities of CCA cell lines, QBC 939 and HCCC-9810 were treated with TUG-891 (a GPR120 agonist) and AH7614 (a GPR120 inhibitor). Results: Both GPR120 and NGF were found to be upregulated in CCA tissues, correlating with aggressive clinicopathological features. IHC staining revealed cytoplasmic localization of GPR120 and NGF, with significantly higher expression in cancerous tissues compared to adjacent noncancerous samples. Among the 386 patients, PNI was observed in 339 (87.8%). PNI correlated with tumor diameter, CA 19-9 levels, TNM stage, preoperative bilirubin levels, tumor differentiation, and preoperative drainage. Notably, GPR120 expression increased in poorly differentiated tumors and advanced clinical stages, indicating a clinical association with CCA progression. In vitro studies demonstrated that GPR120 promoted invasion and migration in the QBC 939 and HCCC-9810 cell lines. Western blot analysis confirmed elevated GPR120 levels in these lines, which also exhibited higher NGF expression. The GPR120 inhibitor AH7614 significantly reduced invasion in QBC 939 and HCCC-9810 cells, while the GPR120 agonist TUG-891 showed no effect on any of the CCA cell lines tested. Conclusions: GPR120 and NGF are implicated in perineural invasion (PNI) in CCA, with a notable correlation between GPR120 and NGF in the context of PNI occurrence.

NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression.

Pancreatic cancer liver metastasis is an important factor leading to dismal prognoses. The details of adaptive immune remodeling in liver metastasis, especially the role of neutrophils, remain elusive. Here, combined single-cell sequencing with spatial transcriptomics results revealed that liver metastases exhibit more aggressive transcriptional characteristics and higher levels of immunosuppression compared with the primary tumor. We identified neutrophils_S100A12 (S100 calcium binding protein A12) cells as the pivotal pro-metastatic cluster, specifically distributed at the invasive front of the metastatic lesions. Mechanistically, our findings indicated that nuclear factor erythroid 2 (NFE2) is a key transcription factor regulating neutrophil phenotypic polarization. Metastatic tumors produce transforming growth factor β to activate the SMAD3 pathway within neutrophils, inducing NFE2-driven polarization. NFE2 promotes the transcription of peptidylarginine deiminase 4 by binding to its promoter, leading to the generation of neutrophil extracellular traps at the invasive front. Collectively, our data demonstrate that NFE2-driven neutrophil polarization is a potential target for anti-metastatic therapy.

Comparison of textbook outcomes between laparoscopic and open liver resection for patients with hepatocellular carcinoma: a multicenter study.

We aimed to clarify whether laparoscopic liver resection (LLR) is better than open liver resection (OLR) concerning textbook outcome (TO) achievement for patients with hepatocellular carcinoma (HCC). Data from HCC patients who underwent liver resection from a multicenter database were retrospectively reviewed (n = 2617). Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups. Logistic regression analysis was performed to identify the risk factors that are independently associated with TO. Before PSM, more aggressive biological characteristics were observed in patients who underwent OLR. After PSM, 771 patients in each group were matched. The overall rate of TO achievement in patients with LLR (78.2%) was higher than that in patients with OLR (71.7%; P < 0.001) after PSM. Subgroup analysis further revealed that LLR was associated with a greater incidence of TO achievement than OLR was in patients who underwent minor liver resection (after PSM; LLR: 83.8% vs. OLR: 73.0%, respectively; P < 0.001) but was similar in those who underwent major liver resection (after PSM; LLR: 68.8% vs. OLR: 65.7%; P = 0.468). Multivariate logistic regression analysis suggested that the LLR (OR = 0.471, 95% CI 95% CI = 0.361-0.614, P < 0.001) was an independent protective factor against non-TO in patients who underwent minor liver resection but not in those who underwent major liver resection. After PSM, the 5-year overall survival (OS) rates of patients who underwent OLR (74.6%) and LLR (73.9%) were similar (P = 0.485). Patients with TO had significantly better OS than those without TO, regardless of whether they underwent LLR (TO: 76.5% vs. non-TO: 65.7%, P = 0.005) or OLR (TO: 76.8% vs. non-TO: 69.1%, P = 0.042). LLR favored TO achievement in HCC patients who received minor liver resection but not in those who underwent major liver resection. Patients who achieved TO had better OS regardless of LLR or OLR.

Tumour hypoxia in driving genomic instability and tumour evolution.

Intratumour hypoxia is a feature of all heterogenous solid tumours. Increased levels or subregions of tumour hypoxia are associated with an adverse clinical prognosis, particularly when this co-occurs with genomic instability. Experimental evidence points to the acquisition of DNA and chromosomal alterations in proliferating hypoxic cells secondary to inhibition of DNA repair pathways such as homologous recombination, base excision repair and mismatch repair. Cell adaptation and selection in repair-deficient cells give rise to a model whereby novel single-nucleotide mutations, structural variants and copy number alterations coexist with altered mitotic control to drive chromosomal instability and aneuploidy. Whole-genome sequencing studies support the concept that hypoxia is a critical microenvironmental cofactor alongside the driver mutations in MYC, BCL2, TP53 and PTEN in determining clonal and subclonal evolution in multiple tumour types. We propose that the hypoxic tumour microenvironment selects for unstable tumour clones which survive, propagate and metastasize under reduced immune surveillance. These aggressive features of hypoxic tumour cells underpin resistance to local and systemic therapies and unfavourable outcomes for patients with cancer. Possible ways to counter the effects of hypoxia to block tumour evolution and improve treatment outcomes are described.

Clinical significance of stratifying prostate cancer patients through specific circulating genes.

Patient stratification remains a challenge for optimal treatment of prostate cancer (PCa). This clinical heterogeneity implies intra-tumoural heterogeneity, with different prostate epithelial cell subtypes not all targeted by current treatments. We reported that such cell subtypes are traceable in liquid biopsies through representative transcripts. Expanding on this concept, we included 57 genes representing cell subtypes, drug targets and relevant to resistance as non-invasive biomarkers for stratification. This panel was tested by RT-qPCR (quantitative reverse transcription polymerase chain reaction) in blood of controls and different categories of PCa patients. Overall, circulating transcripts showed predictive value throughout the disease. Those with aggressive pathological features such as intra-ductal carcinoma at diagnosis showed more genes over-expressed. In metastatic patients, signatures of subtypes or resistance were associated with treatments, progression-free survival and overall survival. Altogether, testing markers of cell diversity, an intrinsic feature of tumours, and drug targets via liquid biopsies represents a valuable means to stratify patients and predict responses to current or new therapeutic modalities. Over-expressed drug target genes suggest potential benefit from targeted treatments, justifying new clinical trials to offer patient-tailored strategies to eventually impact on PCa mortality.

Aggressive characteristics of tumor deposits in colorectal cancer highlight the need for staging refinement in patients with 0-3 metastatic lymph nodes.

Accurate staging is essential for the optimal management of patients with colorectal cancer (CRC). The role of tumor deposits (TDs) in CRC staging has been contentious due to a lack of comprehensive understanding of their clinical and biological traits. In this retrospective study, we analyzed large data from 5718 CRC patients diagnosed between 2011 and 2022, ensuring rigorous data collection and long-term follow-up. Patients with positive TDs displayed aggressive clinical features. The risk factors for TDs varied among patients with different backgrounds of lymph node (LN) involvement, and the numbers of TDs and metastatic LNs showed a significantly positive correlation. TDs significantly impacted CRC prognosis, resulting in unfavorable outcomes irrespective of LN status. To delve into the biological characteristics of TDs, we performed transcriptome sequencing, immunohistochemistry, and Kaplan-Meier analyses on tissue samples from the additional CRC cohort and The Cancer Genome Atlas datasets. TDs exhibited aggressive biological phenotypes that were distinct from primary tumors and metastatic LNs, characterized by elevated signatures of epithelial-mesenchymal transition, angiogenesis, and immune suppression. Cox proportional hazards analysis was then applied to reassess the appropriate role of TDs within the TNM staging system, revealing that the prognostic weightiness of TDs in CRC corresponded to N2a rather than N1 in patients with 0-3 LN metastases. Overall, our comprehensive analysis showed that TDs, with their aggressive clinical and biological characteristics, could optimize the staging of CRC, highlighting the need to refine their role within the TNM staging system.

THE ROLE OF BRAF V600E IN THE DEVELOPMENT OF THYROID CANCER PHENOTYPE: A SYSTEMATIC REVIEW

BRAF V600E mutation in thyroid cancer is of major concern because it is associated with increased tumor aggressiveness through the MAPK pathway activation that affects phenotypic characteristics such as morphology and tissue invasion patterns. The results of studies on the effects of this mutation often vary and are influenced by differences in study design and detection methods. This systematic review aims to clarify the relationship between BRAF V600E and phenotypic characteristics of PTC, as well as identify its clinical implications. This study method was a systematic literature review using the PRISMA method, and there were 8418 journals. After exclusion, 16 articles were found that met the research objectives. Based on the results, it was found that there was a relationship between BRAF V600E and thyroid cancer phenotypes such as female gender, older age at diagnosis, larger tumor size, histological subtypes, especially tall cell, higher nuclear score, capsule, extrathyroid, vascular, nerve invasion, lymph node metastasis, higher clinical stage, recurrence, and lower survival. However, there are other inconsistent studies regarding the association of BRAF V600E with these phenotype characteristics. BRAF V600E mutation significantly affects the phenotypic characteristics of thyroid cancer and is associated with several aggressive characteristics.

Clinicopathological characteristics and survival outcomes of women aged ≤45 and >45 years with endometrial adenocarcinoma in tertiary referral hospital: a 21-year cohort study

ObjectiveThis study aimed to compare clinicopathological characteristics and oncological outcomes in patients with endometrial cancer aged ≤45 and >45 years, with a focus on identifying distinct traits and prognostic factors...

Nanosize Non-Viral Gene Therapy Reverses Senescence Reprograming Driven by PBRM1 Deficiency to Suppress iCCA Progression.

Polybromo-1 (PBRM1) serves as a crucial regulator of gene transcription in various tumors, including intrahepatic cholangiocarcinoma (iCCA). However, the exact role of PBRM1 in iCCA and the mechanism by which it regulates downstream target genes remain unclear. This research has revealed that PBRM1 is significantly downregulated in iCCA tissues, and this reduced expression is linked to aggressive clinicopathological features and a poor prognosis. Furthermore, it is demonstrated that PBRM1 can impede iCCA progression, and a gene therapy nanomedicine is developed to treat iCCA in vivo by modulating PBRM1 expression. The heightened expression of PBRM1 induces by the nanomedicine substantially inhibited tumor growth in iCCA. Conversely, the decrease in PBRM1 results in the abnormal activation of the ERK1/2 signaling pathway, a reduction in p16, p53/p21, and cellular senescence, thereby promoting iCCA advancement. Treatment with U0126, an ERK1/2 inhibitor, effectively halted iCCA progression by regulating the PBRM1-ERK1/2-cellular senescence pathway. These findings underscore the significant role of PBRM1 in controlling iCCA progression and predicting prognosis. Targeting the PBRM1-ERK1/2-cellular senescence pathway with U0126 shows promise for clinical applications in treating iCCA.

Targeting Fibroblast-Derived Interleukin 6: A Strategy to Overcome Epithelial-Mesenchymal Transition and Radioresistance in Head and Neck Cancer.

Cancer-associated fibroblasts have been reported to play a central role in driving cancer progression, promoting metastasis, and conferring resistance to therapy in HNSCC. Indirect and direct co-culture models of HPV-positive and HPV-negative HNSCC cells with fibroblasts were developed to study the effect of fibroblasts on cancer cells. ELISA was used to measure IL-6 secretion in these models. To dissect the underlying signalling mechanisms, the effects of IL-6, an IL-6 receptor (IL-6R) inhibitor, a MAPK/ERK inhibitor, and a JAK/STAT inhibitor were evaluated. Epithelial-to-mesenchymal transition (EMT) was assessed by measuring EMT markers and conducting scratch assays and spheroid assays. Radioresistance was evaluated using clonogenic assays. Additionally, radioresistant (RR) cell lines were established from parental cells to examine the correlation between radioresistance and EMT. Fibroblasts were found to drive EMT-like changes and heightened radioresistance in HNSCC cells through IL-6 secretion. Remarkably, these Fb-driven effects were robustly reversed using IL-6R and MAPK/ERK inhibitors in both HPV-positive and HPV-negative cell lines, whereas JAK/STAT inhibitors proved effective only in HPV-negative cells. RR cell lines exhibit a more aggressive phenotype than their parental counterparts, marked by pronounced EMT features and heightened resistance to radiotherapy. Importantly, these aggressive characteristics were substantially attenuated by targeting IL-6R or MAPK/ERK pathways. This study highlights the critical role of fibroblast-secreted IL-6 in driving and maintaining EMT and radioresistance in HNSCC, resulting in a more aggressive tumour phenotype. Targeting the IL-6/IL-6R/ERK pathway emerges as a promising therapeutic approach for combating CAF-driven tumour progression and improving clinical outcomes in patients with aggressive, therapy-resistant HNSCC.

Reflecting on the impact of the COVID pandemic on patient management and its subsequent influence on long-term outcomes: a case–control study in the field of esophago-gastric cancer

BackgroundThe delivery of cancer services changed significantly during the COVID-19 pandemic. This study aimed to describe changes in presentations, assess the change in recommendations by the MDT during the pandemic, and describe the subsequent long-term impact of these changes on survival rates in patients with EG cancer.MethodsA retrospective cohort study was designed comparing three patient groups of those referred to EG MDT in the same 6-month period pre-pandemic (PP;2019) during the initial phase of the pandemic (P1;2020) and the year after the initial phase (P2;2021). The primary aim of this study was to describe and compare deviations from the standard of care across these three timeframes. Secondary outcomes included differences in the number of new cases with early and advanced oesophageal and gastric lesions, a comparison of survival rates among the groups, and an analysis of postoperative histopathology to identify any shifts in the tumour stage across the studied periods.ResultsA consistent demographic profile across these periods was maintained, but with a significant decrease in patient referrals during P1 (35.25% reduction from PP to P1 and 9.5% reduction from PP to P2), quicker ‘time to treatment’ during P1 (130.8 days in P1 vs 162 in PP and 178.9 in P2), and notable changes in treatment modalities. Additionally, we found an increased deviation from initial curative to palliative intent in the P2 group (6.4% changed in P2 vs 2.2% in PP and 3.5% in P2) primarily driven by disease progression. A further significant observation was the emergence of more aggressive tumour characteristics, particularly in the P2 group, albeit without a statistically significant difference in two-year overall survival rates among the groups (p-value 0.31).ConclusionThe COVID-19 pandemic significantly impacted oesophagogastric cancer care, with a reduction in patient referral rates during the initial pandemic phase and a subsequent increase in more advanced stage disease. Our findings from a major UK EG centre highlight accelerated treatment decision-making during the initial pandemic phase was possible and that standard of care was maintained. These insights provide valuable lessons for healthcare systems in managing cancer care during global health emergencies.

Metabolic Reprogramming in Prostate Cancer: The Roles of HOXB13 and FASN in Tumor Progression and Therapy

Metabolic reprogramming, particularly lipid metabolism, is a hallmark of cancer progression and a critical vulnerability in prostate cancer (PCa). Two pivotal studies, one by Lu et al. and the other by Dairo et al., have illuminated the roles of HOXB13, a transcriptional regulator, and fatty acid synthase (FASN), a key enzyme in lipid biosynthesis, in the metabolic dysregulation of PCa. The Lu et al. study highlights HOXB13’s role in androgen receptor (AR)-independent PCa, where it regulates lipid metabolism via epigenetic mechanisms involving histone deacetylase HDAC3. A G84E mutation in HOXB13 disrupts this regulation, leading to increased lipid synthesis and a pro-metastatic phenotype. The Dairo et al. study demonstrates that FASN hypomethylation, coupled with increased expression, drives lipid biosynthesis critical for tumor growth. Both studies establish a link between HOXB13 mutations and FASN dysregulation, underscoring their interplay in PCa biology. Therapeutically, pharmacological inhibition of FASN mitigates the aggressive features of HOXB13-deficient or mutant PCa, highlighting lipid metabolism as a promising target. Despite their strengths, including robust methodologies, limitations include reliance on preclinical models and the need for broader patient diversity. These studies collectively emphasize the potential of metabolic and epigenetic interventions for precision medicine in PCa, paving the way for novel therapies targeting lipid metabolism in patients with specific genetic and epigenetic profiles.

Relationship between DLK-1 levels in blood serum and survival of patients with glioblastoma

Several studies have shown that the increased expression of delta–like noncanonical Notch ligand 1 (DLK-1) is associated with more aggressive tumor characteristics in patients with glioblastoma. The aim of the study was to estimate the diagnostic and prognostic values of DLK-1 serum levels in glioblastoma patients. Material and Methods. The study included 39 patients with newly diagnosed glioblastoma. The DLK-1 level was evaluated in paired serum and cerebrospinal fluid samples in glioblastoma patients before starting chemoradiotherapy (CRT). All patients with glioblastoma received combined modality treatment. The DLK-1 level in blood serum was additionally assessed during follow-up visits. Results. The median levels of DLK-1 in paired CSF and serum samples before CRT were 1.17 ng/ml (95 % CI 0.78; 2.89) and 0.27 ng/ml (95 % CI 0.26; 0.29), respectively (p=0.006). The assessment of the DLK-1 serum level in glioblastoma patients didn’t show any significant differences related to the response to therapy. In patients with tumor progression after CRT, the median serum DLK-1 level before CRT was 0.43 ng/ml, and in patients with stable disease, the median serum level was 1.7 ng/ml (p=0.012). The DLK-1 serum levels were 1.60 ng/ml and 0.32 ng/ml in patients with favorable prognosis for progression–free survival and in patients with unfavorable prognosis, respectively (p=0.005). The median concentrations of DLK-1 in serum before starting CRT were 1.01 ng/ml and 0.32 ng/ml in patients with favorable prognosis of overall survival and in patients with unfavorable prognosis, respectively (p=0.04). The DLK-1 levels in 4 weeks after CRT were 1.53 ng/ml and 0.23 ng/ml in patients with favorable prognosis of overall survival and in patients with the unfavorable prognosis, respectively (p=0.04). Conclusion. The DLK-1 serum level in patients with glioblastoma cannot be used to diagnose disease progression. However, this marker is a prognostic factor for overall and progression-free survival, and allows identification of patients with favorable and unfavorable prognosis.