The tumor microenvironment in colorectal cancer (CRC) is marked by a diverse and abundant population of cancer-associated fibroblasts (CAFs), which play a crucial role in radioresistance. Nonetheless, the mechanisms through which CAFs contribute to radioresistance remain unclear. In this study, we demonstrate that CAFR, a specific subset of CAFs derived from radioresistant CRC patients, produces higher levels of transforming growth factor-β1 (TGF-β1) compared to CAFs isolated from radiosensitive CRC patients. Through long noncoding RNA (lncRNA) profiling of tumor cells treated with CAF-conditioned medium (CAF-CM), we identify WARS2-IT1 (WARS2 intronic transcript 1), whose expression is directly stimulated by TGF-β1 signaling. This lncRNA serves as a key player in promoting radioresistance and is essential for the TGFβ1-induced radioresistance pathway. Mechanistically, WARS2-IT1 interferes with the interaction between prolyl hydroxylase domain 2 (PHD2) and hypoxia-inducible factor-1α (HIF-1α), preventing the hydroxylation and subsequent degradation of HIF-1α. This process leads to the activation of glycolytic pathways, thereby enhancing radioresistance. Our findings underscore the potential of targeting CAF-driven WARS2-IT1 as a promising strategy to counteract tumor radioresistance in CRC.

This review has been written with the intention of explaining to the patients with ALK-positive lung cancer, and to their families, friends, carers and medical teams, in simple terms, the fundamentals, and the current state of knowledge of this particular type of cancer. The review begins with basic facts about lung anatomy and lung cancer, then explains general principles of how cell proliferation is regulated at the molecular level. The coverage of the molecular events underlying the development of ALK-positive lung cancer and principles of targeted therapies then follows. The review concludes with an analysis of various therapeutic approaches to treat ALK-positive lung cancer. The Supporting Information section contains additional advanced information illustrating specific points of interest.

We aimed to explore the effect of PHLDA2 on the biological behavior of ovarian cancer (OC) cell in vitro.

Lynch syndrome (LS) carriers have a 20-46% lifetime risk of colorectal cancer (CRC) due to mismatch repair gene variants. Mesalamine (5-ASA, 5-aminosalicylic acid), used safely in patients with ulcerative colitis, may reduce CRC risk in LS by decreasing microsatellite instability, a key driver of LS-related cancer. This study evaluates 5-ASA's efficacy as a tolerable chemopreventive drug, aiming to improve long-term CRC prevention in LS.

Despite substantial research investments aiming to prevent cancer and develop therapeutic interventions, cancer remains a formidable challenge. In view of the persistent rise in cancer prevalence, the condition should also be recognised as a chronic disease. Such an approach can enhance the quality of life of patients with cancer, inhibit treatment-related adverse events and prevent recurrence via comprehensive post-treatment management. The core objective of this study is to investigate the association between dietary factors and treatment-related adverse events in patients with cancer, with the aim of providing individualised dietary recommendations to reduce adverse events and enhance quality of life.

Infant-type hemispheric gliomas (IHGs) are extremely rare, large, hemorrhagic tumors of the cerebral hemispheres commonly diagnosed during infancy. Treatment of IHG has been adapted from historical clinical trials that enrolled infants with high-grade glioma (HGG) and involves maximal safe surgical resection followed by adjuvant chemotherapy. With this treatment, IHGs have shown good overall survival rates in retrospective studies; however, survivors have poor long-term neurologic and neurocognitive outcomes because the clinical course is fraught with high rates of surgical morbidity, acute intracranial hemorrhage, tumor progression, and use of multiple chemotherapy regimen for treatment. At the molecular level, IHGs are uniquely driven by RTK fusions, and their DNA methylation profiles distinguish them from other pediatric-type diffuse HGGs while clustering more closely with low-grade desmoplastic infantile ganglioglioma/astrocytoma. Although RTK fusions render IHGs targetable by tyrosine kinase inhibitors (TKIs), their optimal role in infants is yet to be determined. Consequently, TKIs are most often used in the recurrent setting, while surgery and chemotherapy continue to represent the standard primary treatment approach. This review summarizes historical clinical trials, delineates the histopathologic and molecular landscape of IHG, and highlights current therapeutic gaps, underscoring the need for collaborative research efforts to establish standardized treatment approaches.

This study investigates the causal relationship between circulating inflammatory proteins and cervical cancer risk in European and Asian populations using Mendelian randomization (MR), providing insights into inflammation's role in cervical cancer pathogenesis.

Anorectal mucosal melanoma (AMM) poses a significant challenge as a rare and aggressive cancer with limited treatment options. The current standard treatments for AMM have notable drawbacks, often leading to disease recurrence and progression, ultimately resulting in a poor prognosis for patients with advanced AMM. The critical necessity for innovative therapeutic strategies to enhance outcomes in AMM cases is evident. In this report, a groundbreaking personalized (n) of one approach was detailed for the treatment of advanced mucosal melanoma. This pioneering method involves utilizing low-dose immunotherapy as an immune regenerative medicine (IRM) regimen. The treatment plan is tailored based on liquid biopsy analysis of plasma-derived cell-free circulating tumor DNA (ctDNA) with mutational profiling. This approach aims to enhance the patient's immune response to the disease, reduce tumor burden, and minimize adverse effects. This compelling case study showcased a 66-year-old male with recurrent stage III AMM. Despite undergoing standard therapies with multiple surgeries, radiation therapy, and immune checkpoint inhibitor (ICI) treatment, disease progression persisted. However, post low-dose interleukin-2 (IL-2) immunotherapy, notable improvements were observed in the patient's immune function, particularly in natural killer (NK) cell number and activity. Additionally, the cancer exhibited regression, highlighted by a significant decrease in NRAS Q61R driver mutations and the absence of the BRCA2 A3012P mutation. These encouraging results suggest that personalized precision immunotherapy focusing on NK cells could potentially revolutionize the treatment landscape for AMM patients who have exhausted conventional therapies. Notably, the patient experienced minimal side effects and avoided toxicity-related complications. While further research is essential to validate these findings, the prospect of this approach as a viable management strategy for this aggressive cancer type is promising.

Neuro-oncology is the study of brain and spinal cord neoplasms. Molecular targets and signaling pathways are pivotal in advancing modern healthcare, particularly in personalized medicine. Signaling pathways, which regulate cellular processes such as growth, division, and survival, are frequently dysregulated in cancer. Targeting these pathways has enabled the development of personalized therapies that improve efficacy while minimizing side effects. This approach has led to significant improvements in patient outcomes, reduced treatment toxicity, and a shift toward precision medicine, driving innovation in drug discovery. The integration of molecular targets and signaling pathways into clinical practice highlights their importance for enhancing patient care.

Numerous genes have been associated with colorectal cancer (CRC) treatment in prior studies, but the impact of radiotherapy-related autophagy genes (RRAGs) on CRC remains largely unexplored. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were implemented to screen out RRAGs significantly associated with survival, and a prognostic model was constructed. Samples were categorized into high- and low-risk groups with median riskscore. Immunomicroenvironment analysis, immunotherapy response prediction, enrichment analysis, tumor mutation analysis and drug prediction were performed in risk groups. Expression of signature genes in CRC cells was examined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). There were 10 CRC-related RRAGs found. Prognostic models were built with RRAGs. Based on immune infiltration analysis, low-risk populations showed significantly greater levels of immune infiltration (P P ARHGEF17 mutation rate was 6%. Medications such as CGP-082996, Dasatinib, Erlotinib, and Salubrinal were more sensitive to high-risk group, whereas drugs such as FTI-277, DMOG, and Crizotinib were more sensitive to low-risk group. UGT1A6 and IRGM were significantly upregulated in tumor group as revealed by qRT-PCR. This study constructed a new prognostic model for CRC patients based on RRAGs, and a series of analysis results is conducive to providing more theoretical references and new insights into precision treatment of CRC patients.

Lung adenocarcinoma (LUAD) is one of the most malignant tumors with significant implications for population health and life. Nicotinamide metabolism may play a pivotal part in influencing the prognosis of LUAD. This study aimed to figure out the potential value of nicotinamide metabolism-related genes (NMRGs) in LUAD prognosis.

Targeting PI3K/AKT/MTOR (PAM) signaling pathway may be a strategy at the fore for treating lung squamous cell carcinoma (LUSC). However, relationships of PAM pathway-related genes (PAGs) with LUSC prognosis are unknown. Therefore, identifying the prognostic significance of PAGs for LUSC is innovative and feasible. Transcriptomic data, clinical features, and PAGs of LUSC were obtained from public databases (TCGA, GEO). A PAGs-based prognostic model was built using regression analysis in TCGA-LUSC. Gene levels were assessed via qRT-PCR. Predictive performance was verified through multiple datasets. Differences in immune infiltration and anti-tumor immunity between risk groups were assessed by R packages. Sensitivity to common anti-cancer agents was tested using oncoPredict package. We identified a Riskscore model containing 11 PAGs. Patients were assigned into groups of high risk (HR) and low risk (LR) per median Riskscore. CAB39L, CDKN1A, and ITPR2 were significantly underexpressed in LUSC cells. TRAF2 and TRIB3 were significantly enhanced in LUSC cells. The LR group had a longer survival time. Prognostic values of one-, three-, and five-year ROC curves were good. Results were verified in GEO. Patients in LR group had higher immune infiltration levels of B cells and Tfh cells, and higher ssGSEA scores for APC_co_inhibition and T_cell_ co_stimulation. LR group had lower TIDE scores and lower IC50 values (Alpelisib, Ibrutinib, Sapitinib, and Savolitinib). We successfully built a reliable 11-gene Riskscore prognostic model. Patients in LR group had potential advantages in survival, immune response, and drug sensitivity. In summary, the results offered new insights into prognosis prediction, immunotherapy, and personalized treatment of LUSC.

Circular RNAs (circRNAs) play a pivotal part in the advancement of multiple tumors. Nonetheless, the influence of Helicobacter pylori (H. pylori) infection on the expression of circRNA in gastric cancer remains less studied.

Minimal residual disease (MRD) is a small group of cancer cells not eliminated by anti-cancer treatment. Because of its small size, conventional imaging system may not be able to detect the MRD in routine clinical practice. Although the liquid biopsy tests can detect the circulating tumor DNA (ctDNA) when the tumor is present in the body, the fraction of ctDNA is considered lower than the 0.01% which is unreachable by current state-of-the-art liquid biopsy assay relying on fixed-gene panel approach. Here, we describe the analytical validation result of our previously developed a tumor-informed MRD test, CancerDetectTM (formerly reported as AlphaLiquid®Detect), leveraging large-scale mutation spectrum profiling strategy to enhance detection sensitivity. The CancerDetectTM is a hybrid-approach MRD test combining both personalized (bespoke) mutations and tumor-agnostic clinically actionable targets (hotspot mutations) with hybridization capture technology. The analytical validation result of CancerDetectTM showed limit of detection successfully reached down to 0.001% (10-5) with 99.9% specificity.

IntroductionImmune checkpoint inhibitors plus chemotherapy has become the new standard of care for advanced biliary tract cancer (BTC). However, the real-world effectiveness and safety of this approach, and its association with molecular alterations, remains uncertain.MethodsIn this single institutional retrospective cohort study, patients with advanced BTC treated with systemic chemotherapy with or without immunotherapy from July 2020 to June 2025 were included. Primary endpoint was overall survival (OS) in patients treated with first-line chemoimmunotherapy; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, prognostic factors, and molecular profiling.Results49 of 52 patients (94.2%) received chemoimmunotherapy. Median OS and PFS were 10.2 months and 5.4 months, respectively; the ORR was 24.5%. Poor Eastern Cooperative Oncology Group (ECOG) performance status and hypoalbuminemia were independent predictors of poor OS. Among the 52 patients, molecular profiling identified IDH1 mutations (9.6%), FGFR2 fusions (3.9%), HER2 amplification (5.8%), dMMR (5.8%), and BRCA mutations (5.8%). HER2 amplification was associated with worse OS; dMMR and BRCA mutations showed a trend toward improved OS.ConclusionReal world first-line chemoimmunotherapy for advanced BTC achieved outcomes comparable to those in pivotal trials. The ECOG performance status, serum albumin level, and HER2 status were prognostic for OS, supporting the importance of baseline patient selection and molecular profiling in treatment planning.

ObjectivesThis study aims to investigate the significance of tumor microenvironment (TME)-related genes and signal transduction pathways in head and neck cancer (HNC).MethodsGene expression and clinical data of HNC patients were obtained from the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were screened through a multi-step filtration approach to obtain candidate predictors. The biological role of COL5A1 in HNC was verified through rigorous bioinformatic analysis, experimental validation using quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) analysis from HNC samples, and IHC data from the Human Protein Atlas (HPA) database.ResultsCOL5A1 was significantly upregulated in HNC tissues and cell lines. High COL5A1 expression was significantly associated with advanced tumor grade (P < .05) and shorter survival (TCGA: P < .001; GSE42743: P = .004). COL5A1 was an independent prognostic indicator (univariate analysis: HR = 1.324, P = .001; Multivariate analysis: HR = 1.326, P = .005). It was enriched in pathways related to tumor invasion and immune responses, and its expression was associated with decreased levels of CD8+ T cells and increased levels of macrophages and neutrophils. Spatial distribution analysis revealed higher expression at the tumor's leading edge (vs. tumor core: P < .001). COL5A1 expression is associated with tumor stage, with more pronounced expression in advanced-stage tumors.ConclusionCOL5A1 represented a novel potential prognostic indicator and therapeutic target in an HNC database sample, as its expression is closely linked to tumor progression, immune cell infiltration, and adverse clinical outcomes. These findings, primarily derived from squamous cell carcinoma-dominated cohorts, warrant further functional validation.

Super-enhancers (SEs) are clusters of enhancers with potent regulatory capabilities. They play a crucial role in shaping cellular identity and driving the progression of various diseases, including cancer. SEs exhibit significant heterogeneity across different cell types and cancer subtypes. Analysis of SE landscapes can recapitulate existing classification systems and unveil novel SE-driven epigenetic subtypes. In this review, we summarized the latest advancements in cancer subtype identification based on SE-related characteristics, outlined the typical analytical workflows adopted in such studies, and explored the biological and clinical significance of SE-driven subtypes. Furthermore, we discussed the field's key challenges and emerging technologies to highlight future research directions. SE analysis provides a robust framework for dissecting cancer heterogeneity. This approach offers novel epigenetic perspectives and support for the realization of personalized medicine.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a poor prognosis, thus emphasizing the need for early and accurate diagnostic tools. In this study, we propose a comparative study approach to understand how machine learning (ML) modeling using urinary biomarkers combined with demographic data can predict PDAC. The study also utilized a single-cell RNA sequencing (scRNA-seq) analysis to assess and understand gene expressions of included biomarkers. With inclusion of available biomarkers and incorporation of demographic information, we employed different approaches for preprocessing techniques, normalization approaches, ML techniques, and deep learning (DL) approaches to provide a comprehensive prediction model. The scRNA-seq approach also highlighted the significance of the urinary biomarkers from the pancreatic single-cell sample. Based on this analysis, the marker was identified as one of the top three most highly expressed genes in PDAC tissues. The predictive modeling approach was conducted for both binary and multiclass classification using both ML and DL approaches. The comparative analysis using all included parameter combinations produced modeling settings, and among these parameters, the DL modeling approach using binary classification outperformed the other approaches by achieving 91% accuracy. This framework provided insights that highlighted the critical role of demographic data and potential approaches to include such features in the model without impacting the predictive accuracy. Future work will focus on examining the framework using different datasets, integrating additional omics data, and exploring advanced DL architectures to further improve predictive performances.

Adamantimoma-Like Ewing Sarcoma (ALES) is a rare variant of Ewing sarcoma that poses significant diagnostic challenges in the head and neck due to morphologic overlap with basaloid carcinomas and neuroendocrine neoplasms.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive endocrine malignancies, characterized by rapid progression, extensive metastasis, and extremely poor prognosis. Despite advances in molecular oncology, the mechanisms driving ATC metastasis and therapeutic resistance remain largely unclear. Cancer cells that detach from the extracellular matrix must evade a specific form of apoptosis known as anoikis, and the ability to survive under these anchorage-independent conditions is a critical prerequisite for metastatic dissemination. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a master regulator of oxidative-stress responses and tumor adaptation, yet its function in governing anoikis resistance in ATC is not well understood. Here we demonstrate that Nrf2 expression is markedly upregulated in ATC tissues and cell lines, where its nuclear translocation drives transcriptional activation of anti-apoptotic and redox-protective genes including BCL-2 and SLC7A11. Under detachment stress, Nrf2 activation enhances cell viability, inhibits apoptosis, and facilitates multicellular aggregate formation, thereby promoting survival. Conversely, genetic silencing or pharmacological inhibition of Nrf2 with Brusatol markedly suppresses proliferation, invasion, and in vivo liver metastasis. Collectively, these findings identify Nrf2 as a pivotal driver of ATC anoikis resistance and metastatic competence through regulation of the BCL-2/SLC7A11 axis. Targeting the Nrf2-dependent survival pathway may thus offer a promising therapeutic strategy for this otherwise refractory malignancy.