Radioresistance of adenocarcinoma cells limits the efficiency of radiotherapy. In addition to the cell nucleus, ionizing radiation (IR) also induces damage to the mitochondria. Mitophagy, a selective degradation of impaired mitochondria via autophagy, has been found to respond to IR, but its role in the radiosensitivity of adenocarcinoma cells remains unclear. Using several different adenocarcinoma cell lines, we confirmed that exposing the adenocarcinoma cells to 5 Gy X-ray enhanced the expression of some mitophagy receptors and increased mitophagy activity. However, pharmacological inhibition of mitophagy by mdivi-1 did not significantly change the radiosensitivity of HCT116 and A549 cells. Similarly, molecular targeting inhibition of mitophagy by BNIP3L knockdown in HCT116 and A549 cells that showed significant IR-induced BNIP3L up-regulation did also not significantly affect the radiosensitivity of adenocarcinoma cells, although the IR-induced enhancement of mitophagy activity was effectively suppressed. According to our data, mitophagy is responsible to IR but plays a very limited role in the radiosensitivity of adenocarcinoma cells. Further in vivo studies are warranted to elucidate the radiosensitizing effect of targeting mitophagy on malignant tumors.

For over 70 years, methotrexate (MTX) has remained a first-line chemotherapeutic agent for acute lymphoblastic leukemia (ALL), playing a pivotal role in maintenance therapy. Understanding the genetic determinants of MTX efficacy is therefore essential for improving clinical outcomes. However, studies on MTX efficacy-related polymorphisms remain limited, particularly for non-coding variants, for which most evidence is based on statistical associations. Here, through integrative bioinformatics analysis and systematic meta-analysis, we identified rs1544105, a non-coding SNP in the folylpoly-γ-glutamate synthetase (FPGS) gene, as closely associated with MTX efficacy. Compared with the GG genotype, the AA genotype increased disease progression risk (OR: 2.23; 95% CI: 1.16-4.30; p = 0.017) and elevated plasma MTX concentration-to-dose ratios at 24 h (WMD: 2.27; 95% CI: 1.04-4.40; p = 0.002) and 40 h (WMC: 0.02; 95% CI: 0.00-0.04; p = 0.033). Using prime editing, we generated homozygous mutant (GG) 293T cells, demonstrating that rs1544105 A > G increased FPGS expression (~ 1.5-fold, p < 0.05) and intracellular MTX retention (p < 0.05). Moreover, both cell-based and animal experiments confirmed that rs1544105 A > G markedly improved MTX efficacy. Mechanistically, dual-luciferase reporter and electrophoretic mobility shift assays revealed that rs1544105 A > G enhanced the binding affinity of the SNP-containing sequence for the transcription factor CREB1, thereby increasing FPGS transcriptional activity and ultimately augmenting MTX efficacy. Our multidimensional study, integrating data analysis with cellular, molecular, and animal experiments, highlights the remarkable regulatory role of a single SNP, rs1544105, in modulating MTX therapeutic response and provides a basis for individualized MTX-based maintenance therapy in ALL patients.

Acute myeloid leukemia (AML) is characterized by myeloid blasts in the bone marrow and peripheral blood, and it is a highly heterogenous disease genetically. Although our understanding of AML genetics has advanced considerably, disease relapse continues to pose a significant therapeutic hurdle.

To quantify the proportion of HER2-negative metastatic breast cancers with low or ultralow levels of HER2 expression and identify facilitators and barriers to HER2 testing and reporting in US community settings.

The transient receptor potential melastatin (TRPM) family consists of eight members (TRPM1-8), which play a pivotal role in regulating cation fluxes, including K+, Na+, Ca2+, and Mg2+. While these channels are integral to various physiological functions, emerging evidence links TRPM dysregulation to the pathogenesis of colorectal cancer (CRC), one of the most prevalent and deadly malignancies worldwide. This review highlights the multifaceted roles of TRPM channels in CRC pathogenesis, their potential as diagnostic and prognostic biomarkers, and their therapeutic applications. Recent research has revealed that certain types of TRPM channels and specific noncoding RNAs within TRPM loci are implicated in critical oncogenic processes such as proliferation, migration, invasion, and epithelial-mesenchymal transition. Specific members, including TRPM4, TRPM7, and TRPM8, exhibit diverse effects in CRC, ranging from modulating metastasis to influencing chemoresistance. Despite their significant role in CRC, conflicting findings on TRPM expression levels in patient tissues highlight the complexity of their involvement and necessitate further research. TRPM modulators show therapeutic potential as anticancer agents. However, challenges in specificity and off-target effects currently limit their clinical application. Advancing our understanding of TRPM function in CRC could hold promise for novel treatment strategies to improve patient outcomes.

Circulating tumor DNA (ctDNA) enables early detection of ESR1 mutations in hormone receptor-positive, HER2-negative metastatic breast cancer. Building on the PADA-1, the SERENA-6 trial demonstrated significant progression-free survival and quality-of-life benefits from ctDNA-guided early endocrine switching before radiologic progression.

Fluoropyrimidines (e.g., 5-fluorouracil, capecitabine) are antineoplastic agents commonly used in the setting of gastrointestinal cancer. Dihydropyridine dehydrogenase (DPD), encoded by the DPYD gene, is the enzyme responsible for up to 85% of 5-FU catabolism into inactive metabolites. Decreased or no function genetic variations in DPYD are rare but increase risk of potentially fatal adverse effects (e.g., myelosuppression) due to decreased metabolism of 5-FU. The extent of which DPD enzyme activity is impaired varies among individual decreased function DPYD variants.

Lung adenocarcinoma often carries driver mutations, such as EGFR mutations, which are effectively targeted by EGFR tyrosine kinase inhibitors (EGFR-TKIs) like osimertinib, a third-generation EGFR-TKI approved for treating T790M and other EGFR-activating mutations. However, the development of adaptive drug resistance remains a major challenge and is associated with poor prognosis in cancer therapy. Ganoderma microsporum immunomodulatory protein (GMI) has demonstrated anticancer properties in various cancers and exhibits synergistic cytotoxic effects when combined with several anticancer drugs. This study investigated the cytotoxic mechanisms of GMI on the lung cancer cell line H1975, which harbors the EGFR L858R/T790M double mutation, as well as on H1975/TR cells with osimertinib resistance. GMI treatment triggered apoptosis in H1975 cells, as indicated by plasma membrane phospholipid translocation and loss of mitochondrial membrane potential. GMI-treated cells displayed increased LC3BII and the development of acidic vesicular organelles, both of which are hallmarks of autophagy induction. Autophagy inhibition by 3-methyladenine and ATG gene silencing effectively decreased the cytotoxic effect of GMI, suggesting that GMI induces autophagic cell death in H1975/TR cells. This study is the first to reveal the novel role of GMI in inducing cytotoxic effects in H1975 cells and H1975/TR cells with osimertinib resistance through two different forms of cell death: apoptosis and autophagy, respectively.

Given the global high incidence of colorectal cancer (CRC) and the need for subtype-specific molecular targets, this study aims to investigate the role and therapeutic potential of EIF4A1 in colon and rectal cancers.

Non‑small cell lung cancer (NSCLC), accounting for >85% of LC cases, remains a therapeutic challenge due to its low 5‑year survival rate, tumor heterogeneity and drug resistance. The SRY‑related high‑mobility group‑box (SOX) family comprises transcription factors involved in the initiation and progression of NSCLC. These factors regulate epithelial‑mesenchymal transition and angiogenesis, interact with epidermal growth factor receptor/KRAS pathways to influence tumor invasion and promote chemotherapy resistance by sustaining tumor stemness. The present review aimed to summarize the expression patterns, molecular mechanisms and clinical relevance of SOX family members (such as SOX2, SOX4 and SOX9) in NSCLC, as well as their potential as diagnostic biomarkers and therapeutic targets, and the application of emerging technology in elucidating their functions. The present review aimed to provide a theoretical foundation for precision diagnostics and therapeutics to foster more effective NSCLC treatment.

Pancreatic ductal adenocarcinoma (PDAC) resistance to oxaliplatin is associated with diminished drug uptake and a poor molecular apoptotic response; however, the relative contribution of each of these modes of resistance remains unclear. Accordingly, PDAC cell lines (AsPC‑1 and BxPC‑3) and human patient‑derived organoids (hPDOs; h08 and h19) were assessed in the present study, with proliferation assays, atomic absorption spectroscopy‑based quantification of intracellular oxaliplatin, luminogenic caspase 3/7 assays, PCR array‑based transcriptomic analysis and RNA sequencing performed to scrutinize the oxaliplatin resistance phenotype. Notably, AsPC‑1 cells [half maximal inhibitory concentration (IC50), 88.8±45 µM were 4.2‑fold more oxaliplatin resistant than BxPC‑3 cells (IC50, 21±0.7 µM; P=0.02)]. In addition, when normalized to intracellular platinum levels, AsPC‑1 cells remained 2.5‑fold more resistant than BxPC‑3 (the fold difference was decreased by 40% from 4.2‑fold to 2.5‑fold; P=0.21). In hPDOs, resistant h19 took up oxaliplatin 22% less efficiently than sensitive h08, and the nominal resistance difference was 3.5‑fold, and it remained at 2.8‑fold after controlling for drug accumulation (the fold difference was decreased by 20% from 3.5‑fold to 2.8‑fold; P=0.34). These findings indicated that diminished drug uptake non‑significantly contributed to oxaliplatin resistance, which was in agreement with the rather minor differences in drug transporter expression levels (including ATP7A and ATP7B). Furthermore, when challenged with identical intracellular oxaliplatin levels, AsPC‑1 cells exhibited delayed caspase 3/7 activity initiation, weaker induction of pro‑apoptotic genes BBC3 (1.7‑fold vs. 5‑fold) and PMAIP (2.5‑fold vs. 6‑fold), but stronger enhancement of anti‑apoptotic Jun expression (7‑fold vs. 3‑fold) than BxPC‑3 cells. Taken together, oxaliplatin resistance in PDAC models may be highly linked to a poor apoptotic response, whereas drug uptake seems to be of minor relevance.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, for the immunohistochemical data shown in Fig. 2B and C, the PBS/TUNEL panel in Fig. 2B appeared to be strikingly similar to the PBS/E1A panel shown in Fig. 2C. Furthermore, for the E1A experiments portrayed in Fig. 2C, portions of the data panels shown for the H101 and E1A groups also appeared to be strikingly similar, albeit with rotation of one of the panels. The authors were contacted by the Editorial Office to offer an explanation for this possible anomaly in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Oncology 46: 1759‑1767, 2015; DOI: 10.3892/ijo.2015.2852].

Glioblastoma (GBM), the most common type of primary malignant brain tumor, is characterized by aggressive cancer cells that contribute to infiltrative growth, thus resulting in therapeutic challenges and a poor prognosis. To explore the molecular mechanisms underlying cell motility and to identify therapeutic targets that may intervene in tumor invasion, public databases were used to investigate the S100B expression profile and the prognosis of patients with tumors. The effects of S100B on a GBM cell line were assessed through lentiviral transduction, as well as cell viability, colony formation, 5‑ethynyl‑2'‑deoxyuridine‑based cell proliferation, cross‑scratch, and Transwell migration and invasion assays. In addition, a tumor xenograft model was constructed to analyze tumor growth in vivo. Reverse transcription-quantitative PCR, western blotting and immunofluorescence staining were utilized to explore the molecular biological mechanisms of the TGF‑β2‑induced epithelial‑mesenchymal transition (EMT) in the S100B‑downregulated group. The findings demonstrated that S100B was significantly upregulated in GBM samples and was strongly associated with patient prognosis. In vitro and in vivo experiments confirmed that downregulation of S100B effectively suppressed the proliferation and tumorigenicity, as well as decreased the invasive and migratory capabilities of LN229 glioblastoma cells. Further investigation revealed that the inhibition of S100B resulted in downregulation of TGF‑β2 expression and reversal of the EMT process. Notably, recombinant TGF‑β2 restored the cell motility and EMT capacities attenuated by the downregulation of S100B. In conclusion, the present study revealed that S100B may induce the invasion and migration of GBM cells through TGF‑β2‑induced EMT, providing novel insights and potential therapeutic targets for GBM.

Gastric cancer (GC) ranks among the most prevalent malignancies worldwide and is associated with high mortality rates. Ephrin‑B2 (EFNB2), a membrane‑bound ligand that interacts with Eph receptor tyrosine kinases, has been implicated in various cancer‑related biological processes; however, its precise role in GC remains poorly understood. By integrating data from multiple public databases with immunohistochemical analyses of tissue microarrays, significant upregulation of EFNB2 expression in GC specimens compared with paired adjacent normal tissue was demonstrated. Elevated EFNB2 levels were associated with the poor overall survival and disease‑free survival in patients with GC. EFNB2 knockdown inhibited cellular proliferation and viability, increased apoptosis, and induced cell cycle arrest at the G0/G1 phase in GC cells. By contrast, EFNB2 overexpression resulted in the opposite oncogenic effects. Mechanistically, rescue experiments identified the Wnt/β‑catenin signaling cascade as the primary molecular pathway mediating EFNB2‑driven tumorigenic effects. These results were further validated in vivo using cell‑derived xenograft models, which confirmed the key role of Wnt/β‑catenin pathway activation in EFNB2‑induced tumor progression. Collectively, these results suggested that EFNB2 represents a promising molecular target for therapeutic intervention in GC.

Tumor-associated macrophages (TAMs) shape the tumor microenvironment and drive hepatocellular carcinoma (HCC) progression. However, the prognostic significance of TAM polarity-related genes, particularly based on the CXCL9:SPP1 signature, remains unclear.

Solute carrier family 2 member 3 (SLC2A3), a key glucose transporter, has been implicated in tumor metabolism and immune regulation, but its specific role in kidney renal clear cell carcinoma (KIRC) remains largely unclear.

Small cell lung cancer (SCLC) is challenging to manage due to its high malignancy and early metastatic spread. Although initial chemoradiotherapy responses are common, resistance rapidly develops, and long-term efficacy remains limited. Immune checkpoint inhibitors (ICIs) overcome previous survival barriers, extending overall survival (OS) and progression-free survival (PFS) in extensive-stage SCLC. Nevertheless, absolute clinical benefits remain modest. To address efficacy limitations, current research focuses on optimizing first-line strategies by exploring multimodal regimens (e.g., adding targeted therapy or radiotherapy to chemoimmunotherapy) and advancing molecular subtyping for precision oncology. Furthermore, emerging therapies such as DLL3-targeted agents, bispecific antibodies (bsAbs), antibody-drug conjugates (ADCs), and chimeric antigen receptor T-cell (CAR-T) therapy continue to demonstrate clinical progress. This review synthesizes advances in SCLC management, focusing on mechanisms and clinical applications of multimodal strategies and novel therapies. It provides guidance for clinical decisions, research directions, and survival improvement.

Acute myeloid leukemia (AML)-M2b with t(8;21)(q22;q22)/RUNX1::RUNX1T1 (AML1-ETO) is associated with a high risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Post-transplant lymphoproliferative disorder (PTLD), particularly involving the central nervous system (CNS), confers a poor prognosis. Although CD19 chimeric antigen receptor T-cell (CAR-T) therapy is established in B-cell malignancies, its application in acute myeloid leukemia (AML) or CNS-PTLD has rarely been reported.

This study investigates the relationship between the systemic immune-inflammation index (SII) and all-cause mortality (ACM) risk in individuals with stages IIIB-IV epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma.

The prediction of cancer drug responses (CDRs) holds considerable relevance for the guidance of patient-specific clinical treatments. However, the inherent cellular heterogeneity among cancers introduces substantial challenges to such predictions. This paper presents a novel molecular graph convolutional model, named DVFGCDR, developed for predicting CDRs. This innovative model amalgamates both 2D chemical and 3D geometric drug properties to derive a more representative drug embedding. It also includes the capacity to integrate gene expression data from single-cell and bulk RNA sequencing data associated with hundreds of cancer cell lines, thereby enhancing the accuracy of drug response predictions. Experimental comparisons highlight the superior performance of the DVFGCDR model in CDR classification and regression tasks, achieving a Pearson score of 0.959, surpassing current state-of-the-art models. This superiority underscores the model's powerful predictive capability.