Inflammation exerts context-dependent influences on tumor progression and therapeutic response. Although chemotherapy remains a cornerstone of cancer treatment, its functional interplay with inflammatory signaling is still incompletely understood. Here, we identify TANK-binding kinase 1 (TBK1) as a critical modulator of chemotherapeutic efficacy through its impact on DNA damage repair. TBK1 activation potentiates cancer-cell death induced by chemotherapeutic agents by promoting DNA damage and impairing homologous recombination (HR) repair. This effect occurs independently of canonical inflammatory cytokines, as demonstrated in IRF3- and p65- double deficient cells. Mechanistically, TBK1 suppresses recruitment of the key HR factor Meiotic Recombination 11 Homolog 1 (MRE11) to PARP1 at DNA-damage sites in a kinase-activity-dependent yet cytokine-independent manner. Furthermore, TBK1 activation correlates with enhanced p53 signaling and genomic instability, providing a molecular basis for its pro-death effects under chemotherapy. Collectively, these findings reveal a previously unrecognized function of TBK1 in modulating the DNA-damage response, linking inflammatory signaling to genome destabilization and identifying the TBK1-MRE11 axis as a potential target to enhance chemotherapeutic efficacy.

Targeted therapy for BRAF V600E mutant papillary craniopharyngioma (PCP) has been rapidly accepted, though given the rarity of the tumor, there is limited guidance for appropriate use. Here, we retrospectively evaluated current practice patterns for the implementation of targeted therapeutics and their outcomes in the treatment of papillary craniopharyngioma (PCP).

Microsatellite instability (MSI) is a key biomarker for immunotherapy in gastric cancer (GC), but preoperative non-invasive prediction remains challenging. Radiomics is promising; however, a systematic evaluation of its diagnostic performance with explicit consideration of overfitting and model comparison is lacking.

Patients with AML have a poor prognosis due to recurrence and high-risk genetic factors. lncRNA OIP5-AS1 exhibits differential expression among AML patients with varying genetic risks. The aim of this study is to examine the clinical value and regulation mechanisms of OIP5-AS1 in AML. RT-qPCR was used to evaluate the OIP5-AS1, miR-15a-5p, and FOXO1 levels in patients with AML and cells, as well as the mRNA levels of Bcl-2, Bax, and Caspase-3 in AML cell. The CCK-8 test was employed to measure cell proliferation. Apoptosis rates were detected by flow cytometry. DLR experiments validated the interaction between OIP5-AS1, miR-15a-5p, and FOXO1. Compared with the controls, AML patients exhibited notably elevated levels of OIP5-AS1 and FOXO1, along with markedly reduced miR-15a-5p expression. Furthermore, OIP5-AS1 levels effectively differentiate patients with AML from controls. Patients in the high OIP5-AS1 level group exhibited lower 5-year survival rates. Knockdown of OIP5-AS1 elevated miR-15a-5p levels, reduced cell proliferation capacity, and notably increased apoptosis. Furthermore, FOXO1, as a target gene of miR-15a-5p, showed a positive correlation with OIP5-AS1 level and a negative correlation with miR-15a-5p level. OIP5-AS1 exhibits significant diagnostic and prognostic value in AML, showing promise as a novel clinical biomarker. Knockdown of OIP5-AS1 leads to upregulation of miR-15a-5p level, thereby influencing proliferation and apoptosis processes in AML cells. This mechanism may provide a new therapeutic target for improving the prognosis of AML patients.

Machine learning (ML) is transforming cancer research and care by enabling analysis of complex, high-dimensional datasets spanning genomics, transcriptomics, proteomics, imaging, and clinical records. By improving risk stratification, accelerating detection and diagnosis, and supporting treatment selection, ML has the potential to enhance survival outcomes while increasing efficiency across oncology workflows. This review synthesizes key developments in ML for oncology, covering foundational algorithms alongside emerging approaches. We highlight major application areas including early cancer detection, tumor classification, molecular subtyping, biomarker discovery, prognosis estimation, multi-omics integration, computational pathology, pharmacogenomics, and clinical decision support. We also summarize commonly used datasets, discuss the importance of interpretability for clinical trust, and outline barriers to translation such as data heterogeneity, bias, and regulatory constraints. Finally, we describe future directions, including federated learning, graph neural networks, longitudinal modeling, and integration of real-world and wearable data to support precision oncology. This review is intended for cancer researchers, clinicians, and data scientists seeking a practical overview of ML methods, opportunities, and translational considerations in oncology.

Purpose To evaluate the added value of a synthetic radiomics model (S-Radiomics) that integrates topologic and Hessian-based features with traditional radiomic features for predicting a pathologic complete response (pCR) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Materials and Methods Patients with HER2-positive breast cancer from three centers were retrospectively included between January 2018 and January 2024. Patients from centers 1 and 2 (n = 201) were randomly assigned to training (n = 150) and internal testing (n = 51) sets, whereas patients from center 3 (n = 82) constituted external testing set I. An additional genomic set (n = 64, I-SPY 2) and external testing set II (n = 57, I-SPY 1) were used for independent validation. Multivariable logistic regression with all clinical variables was used to identify independent predictors (P < .05) and develop the clinical model, adjusting for potential confounders. Traditional radiomics model (T-Radiomics) and S-Radiomics were constructed. Performance was evaluated using area under the receiver operating characteristic curve (AUC), integrated discrimination improvement, net reclassification index, and survival analysis. Results A total of 404 female patients with HER2-positive breast cancer (mean age ± SD, 50 years ± 9) were included. The S-Radiomics outperformed the T-Radiomics on both the internal (AUC, 0.86 vs 0.78; P = .37) and external test (AUC, 0.84 vs 0.73; P = .11) sets, with improvements in the integrated discrimination improvement (P = .24 and .01) and net reclassification index (P = .21 and .01). Shapley additive explanations analysis revealed topologic features as the most important predictors. For center 1, survival analysis revealed longer disease-free survival in predicted responders (P = .02). Conclusion The S-Radiomics outperformed the T-Radiomics in predicting pathologic complete responses in patients with HER2-positive breast cancer. Keywords: Radiogenomics, MRI, Breast, Human Epidermal Growth Factor Receptor 2, Breast Cancer, Neoadjuvant Chemotherapy, Pathologic Complete Response, Radiomics Supplemental material is available for this article. © RSNA, 2026.

Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy with a poor prognosis. However, the molecular mechanisms underlying CCA and its treatment options remain unclear and limited.

Ovarian carcinosarcoma (OCS) is a rare, aggressive tumor composed of both carcinomatous and sarcomatous components, typically associated with poor prognosis. Due to its rarity, the molecular characteristics, immune microenvironment, and optimal treatment of OCS remain unclear. This study aimed to characterize the genomic profiles, Trop-2 expression, and immune microenvironment of the carcinomatous and sarcomatous components of OCS separately, and to explore candidate therapeutic targets for this rare and aggressive tumor.

The purpose was to investigate whether the eosinophil biomarker EMR1, ectopically expressed in colon cancer tumor cells, could be used to identify patients at risk for relapse after curative surgery. EMR1 mRNA levels were determined in primary tumors (n = 66) and lymph nodes (LNs; n = 377) from 121 colon cancer patients. Controls were resection margins of colon cancer tumors and LNs from patients with inflammatory bowel disease. Primary read-out was recurrency evaluated as disease-free survival time in the Kaplan-Meier survival model and hazard ratio calculation by uni- and multivariate Cox regression. High EMR1 levels in the regional LNs were associated with poor prognosis [hazard ratio 3.1 (1.2-8.0) at 5-year follow-up, p = 0.02]. Patients with a very poor prognosis were identified by combining EMR1 with CXCL17 analysis of LNs [hazard ratio 4.6 (1.1-19.7), p = 0.04]. High EMR1 levels in the primary tumor were associated with a good prognosis [hazard ratio 0.1 (0.02-0.9), p = 0.04]. Multivariate analysis strengthened the result for LNs but weakened the result for the primary tumor. These contradictory prognostic results probably relate to the prominent eosinophilia in the primary tumor, essentially lacking in LNs, where ectopically expressed EMR1 in tumor cells dominates. Thus, EMR1 expressed in tumor cells probably promotes tumor growth.

Neoadjuvant chemoimmunotherapy (NACIT) improves survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), but optimal decisions remain challenging. Clinicopathological factors combined with whole-exome sequencing (WES) and peripheral immune repertoire sequencing (IRS) are promising for identifying prognostic factors to provide insights for clinical decisions and underlying mechanisms.

Hepatocellular carcinoma (HCC) arises in the liver, an organ with active lipid metabolism, and is accompanied by marked myeloid-cell remodeling. Whether lipid-handling macrophage states are enriched in HCC and how they relate to candidate ligand-receptor communication and tumor microenvironmental remodeling remain unclear.

Mast cells (MCs) play important roles in allergic reactions and tissue homeostasis; however, their functions in esophageal squamous cell carcinoma (ESCC) remain controversial. Understanding the heterogeneity and functional states of MCs in ESCC is essential for elucidating their roles in tumor progression and immune regulation.

Histone deacetylase 1 (HDAC1) is frequently dysregulated in various human malignancies; however, the molecular mechanisms underlying its role in non‑small cell lung cancer (NSCLC) remain unclear. HDAC1 expression was evaluated in 157 paired lung adenocarcinoma (LUAD) and adjacent non‑neoplastic tissues using tissue microarray and immunohistochemical analysis. The functional role of HDAC1 was assessed in A549, H1299 and H1975 NSCLC cells following stable knockdown or overexpression, using Cell Counting Kit‑8, colony formation and Transwell assays. Downstream signaling was examined by western blotting and nuclear‑cytoplasmic fractionation. Rescue experiments were performed by overexpressing β‑catenin in HDAC1‑knockdown cells and the findings were further validated in a subcutaneous xenograft tumor model in nude mice. HDAC1 was markedly upregulated in LUAD tissues and associated with lymph node metastasis and poor differentiation. Functionally, HDAC1 knockdown inhibited proliferation, colony formation, migration and invasion in all three NSCLC cell lines. These effects were accompanied by downregulation of c‑Myc, cyclin D1 and vimentin, upregulation of E‑cadherin and reduced nuclear β‑catenin accumulation. Conversely, HDAC1 overexpression enhanced malignant phenotypes and promoted β‑catenin nuclear accumulation. Notably, the phosphorylation of AKT (Thr308 and Ser473) and ERK1/2 remained unaltered following HDAC1 modulation. β‑catenin overexpression effectively eliminated the tumor‑suppressive effects of HDAC1 knockdown both in vitro and in vivo. These findings indicated that HDAC1 is a critical promoter of LUAD progression, acting at least in part through β‑catenin nuclear accumulation. This provided a mechanistic rationale for targeting the HDAC1/β‑catenin axis as a potential epigenetic therapeutic strategy in LUAD.

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy with limited options for early diagnosis and poor clinical outcomes. In the present study, PIWI‑interacting RNA (piR)‑164552 was identified as a novel oncogenic regulator in HNSCC. piR‑164552 was found to be markedly upregulated in tumor tissues and serum exosomes and its expression promoted the proliferation, migration, invasion and tumorigenicity of HNSCC cells both in vitro and in vivo. Mechanistic analyses revealed that piR‑164552 interacted with RNA‑binding motif protein 4 (RBM4) and positively regulated RBM4 protein levels, which in turn enhanced the expression of eukaryotic initiation factor 4E‑like 2 (EIF4E2), forming a piR‑164552/RBM4/EIF4E2 axis. Integrated transcriptomic and translatomic profiling further demonstrated that this axis orchestrated extensive reprogramming of mRNA metabolism, ribosome biogenesis and cancer‑associated signaling pathways, underscoring its multilayered role in tumor progression. The present findings highlighted the diagnostic potential of piR‑164552 and uncovered its key contribution to the molecular network driving HNSCC, providing new insights into biomarker development and therapeutic strategies.

Oxidized low density lipoprotein receptor 1 (OLR1) regulates glycolytic metabolism, lactate production and carcinogenesis, but its role in papillary thyroid cancer (PTC) is still unclear. The present study aimed to investigate the effect of OLR1 modification on PTC cellular functions and its interaction with histone H3 lysine 18 lactylation (H3K18la) and downstream molecular mechanisms. Lectin‑like oxidized low‑density lipoprotein receptor‑1 (LOX‑1; OLR1 coding protein) and H3K18la expression was detected in twenty pairs of PTC and non‑tumor tissues by immunohistochemistry. Overexpressed OLR1 and small interfering (si)RNA were transfected into two PTC cell lines (TPC‑1 and IHH‑4 cells). After which, oxamate (to reduce lactate production) or LEM domain containing 1 (LEMD1) siRNA combined with OLR1 overexpression plasmid was used to treat PTC cell lines. Furthermore, PTC xenograft mice were constructed for in vivo verification. LOX‑1 and H3K18la expression was upregulated in PTC tissues versus non‑tumor tissues and LOX‑1 expression positively associated with H3K18la expression in PTC tissues. OLR1 overexpression facilitated cell proliferation and invasion but repressed cell apoptosis in PTC cell lines, while OLR1 siRNA revealed an opposite effect. OLR1 positively regulated lactate production, H3K18la expression and LEMD1 expression. Furthermore, a chromatin immunoprecipitation assay confirmed a direct binding between H3K18la and the LEMD1 promoter. H3K18la expression was lowered by oxamate‑induced lactate reduction, which also attenuated the effect of OLR1 overexpression on PTC cell proliferation, apoptosis and invasion and downregulated LEMD1 expression. Moreover, LEMD1 siRNA weakened the effect of OLR1 overexpression on PTC cell proliferation, apoptosis and invasion. In vivo experiments revealed that OLR1 overexpression elevated tumor volume and weight and upregulated the expressions of LEMD1 and H3K18la; while LEMD1 knockdown reduced tumor volume and weight. In conclusion, OLR1 promotes PTC proliferation and invasion, while represses apoptosis through regulating H3K18la‑mediated LEMD1.

Following the publication of the above article, a concerned author drew to the authors' attention that, regarding the data showing caspase-3 activity as measured by a colorimetric assay in Fig. 7 on p. 1015, given the use of the MCF‑7 cell line in this study, it was unexpected that the authors would have identified changes in caspase‑3 activity, since it has been demonstrated that MCF‑7 cells do not express caspase‑3 [for example, see the paper by Jänicke and colleagues entitled 'MCF‑7 breast carcinoma cells do not express caspase‑3'. Breast Cancer Res. Treat., vol. 117.1 (2009); p. 219‑221]. In addition, the reader noted that, in the Materials and methods section, it was stated that an Ac-DEVD-pNA-based assay had been used, which has been reported not to be specific for caspase-3, since this assay also reacts to caspase-7 ['Preparation of the caspase-3/-7 substrate Ac-DEVD-pNA via solution-phase peptide synthesis'. Nat Protoc., vol. 5(2) (2010); p. 294-302]. The reader also noted that it was surprising that none of the western blot experiments included in this study actually probed for the presence of the caspase-3 protein, given that the caspase-3 signaling pathway represented one of the principal foci of the study. The authors have been contacted by the Editorial Office to offer an explanation for these apparent anomalies or curiosities in the presentation of the data in this paper, and we are awaiting their response. 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. [Oncology Reports 37: 1011-1019, 2017; DOI: 10.3892/or.2017.5358].

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the Transwell migration and invasion assay experiments shown in Figs. 3D, 6D and F, and 7G and I contained three sets of overlapping sections of data, such that data which were intended to show the results of differently performed experiments had apparently been derived from the same original sources. In addition, the 'si‑FSCN1' data panel for the migration assay experiments shown in Fig. 6D apparently reappeared in Fig. 6 of another paper written by different authors at different research institutes, which was submitted at a later date to the journal Medical Science Monitor. The authors have been contacted by the Editorial Office to offer an explanation for the apparent anomalies in the presentation of the data in this paper, and we are awaiting their response. 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. [Molecular Medicine Reports 22: 5282‑5292, 2020; DOI: 10.3892/mmr.2020.11592].

Metabolic reprogramming is closely associated with the development and progression of cancer and is considered an emerging hallmark of cancer. To meet the bioenergetic and biosynthetic demands, tumor cells tend to initiate the metabolic reprogramming process, creating a tumor microenvironment that is adaptable for cancer cell growth and further promote oncogenic signaling, cell proliferation and metastasis. As a final byproduct of purine metabolism, the uric acid (UA) concentration rises in the quickly growing tumor microenvironment. However, whether elevated UA affects the development and prognosis of patients with tumors has not been demonstrated. In the present study, Cell Counting Kit‑8 and scratch healing test were used to investigate the effects of UA on the proliferation and migration of breast cancer cells. The effects of UA on nucleotide de novo synthesis genes in breast cells were validated using quantitative PCR (qPCR) and western blotting (WB). The activation of stemness in breast cancer cells by UA was validated using colony formation assays, ELISA, qPCR and WB. Finally, clinical data and The Cancer Genome Atlas database were analyzed to examine the expression of de novo nucleotide synthesis genes in cancerous and adjacent tissues, as well as in different types of breast cancer tissues. The present study investigated the potential effect of UA on the function of breast cancer; it also determined how UA affected the genes involved in nucleotide de novo synthesis, as well as how it contributes to tumor stemness. It was discovered that UA could enhance tumor stemness in breast cancer cells through the upregulation of guanosine 5'‑monophosphate synthase (GMPS). It was notable that GMPS expression in patients with breast cancer may be strongly associated with the course of the disease and the prognosis of patients. In conclusion, the present study demonstrated that elevated UA upregulates GMPS and stimulates the migration and proliferation of breast cancer cells through the cyclic guanosine monophosphate/protein kinase G/mitogen‑activated protein kinase pathway axis.

Breast cancer is the most abundant cancer type in female. Genome-wide association study suggests that rs2016394, one SNP at the intron of DLX2 divergent transcript (DLX2-DT), is significantly associated with this disease. Through 1000 genomes project data analysis, it is observed that another three SNPs, rs743605, rs2357322, and rs17726078, show strong linkage disequilibrium with rs2016394. However, the functional SNP(s) and mechanism are still unknown.

Mutant KRAS inhibition has revolutionized the treatment of lung adenocarcinoma. Unfortunately, responses to this form of targeted therapy are often of limited duration because of the development of resistance. Targeted protein degradation, including using PROTACs (PROteolysis-TArgeting Chimeras), presents an alternative approach to targeting oncogenic drivers in cancer. In this issue of Cancer Research, Martín and colleagues developed a dTAG-KRASG12V syngeneic mouse model that allows for the study of the effects of degrading the KRASG12V oncoprotein in vivo. The authors discovered that degrading the KRASG12V oncoprotein leads to regression of the resulting lung adenocarcinoma tumors. Most of the regression was based on cancer cell-intrinsic responses, although the tumor microenvironment also underwent substantial remodeling. Despite the initial efficacy of the treatment, the authors found that prolonged PROTAC KRAS degrader treatment eventually resulted in relapse. Resistance to PROTAC treatment seemed to be driven by dysregulation of the ubiquitin-proteasome system that is required for the activity of the PROTAC degraders. Despite developing resistance to the PROTAC degraders, the resulting tumors were still dependent on the KRAS oncoprotein, meaning that they were still sensitive to conventional KRAS inhibitors. Thus, PROTACs that degrade the KRAS oncoprotein are a promising modality for the treatment of lung adenocarcinomas. Resistance to PROTACs may differ from conventional KRAS inhibitors, suggesting potential strategies for overcoming such resistance. See related article by Martín et al., p. 4115.