Anti-Cancer Drugs最新文献

{"title":"EP4 influences bortezomib resistance in multiple myeloma by modulating endoplasmic reticulum stress via the phosphatidylinositol 3-kinase/protein kinase B pathway.","authors":"Tengfei Shi, Yao Chen, Zhiqiang Liu, Aichun Liu","doi":"10.1097/CAD.0000000000001792","DOIUrl":"10.1097/CAD.0000000000001792","url":null,"abstract":"<p><p>Multiple myeloma, a hematologic malignancy characterized by the uncontrolled proliferation of plasma cells, presents a significant therapeutic challenge, particularly due to the development of resistance to bortezomib, a cornerstone in its treatment. The prostaglandin E receptor 4 (PTGER4 or EP4), a component of the prostaglandin E2 signaling pathway, has emerged as a potential modulator of drug resistance. However, its precise mechanistic role in multiple myeloma remains inadequately understood. This study aims to elucidate the role of EP4 in bortezomib resistance, specifically focusing on its interaction with the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. We employed a comprehensive approach that integrates bioinformatics analysis of multiple myeloma-related genes from public databases with advanced molecular biology techniques. Our investigation examined EP4 expression in both bortezomib-resistant and bortezomib-sensitive multiple myeloma cell lines. The impacts of EP4 overexpression on various cellular processes, including proliferation, apoptosis, endoplasmic reticulum (ER) stress, and bortezomib sensitivity, were examined. Both in vitro and in vivo experiments were conducted to delineate the role of EP4 in modulating the PI3K/AKT pathway and its downstream effects on drug resistance. Our findings revealed a significant decrease in EP4 expression in multiple myeloma tissues, with important implications for patient survival and prognosis. Overexpression of EP4 in bortezomib-resistant cell lines enhanced their sensitivity to the drug, inhibited cell growth, and induced apoptosis. These effects were accompanied by decreased phosphorylation of PI3K and AKT, along with increased expression of glucose-regulated protein 78 000, an indicator of ER stress. Notably, these effects were partially reversed when combined with treatment using an AKT agonist. EP4 plays a significant role in modulating bortezomib resistance in multiple myeloma through its effects on the PI3K/AKT pathway and ER stress. These findings underscore the therapeutic potential of targeting EP4 to enhance bortezomib efficacy and improve clinical outcomes for patients with multiple myeloma.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"280-296"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12955957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy and safety of S-1 plus oxaliplatin with sintilimab vs. paclitaxel-S-1-oxaliplatin and docetaxel-oxaliplatin-5-fluorouracil as first-line therapy for advanced gastric cancer.","authors":"Yicong Wang, Bingyang Ma, Chenguang Zhang, Yuwen Wang, Ting Pan, Chunlong Zhao, Baojia Cai, Pengjie Yu, Bin Guo, Jinfu Ma","doi":"10.1097/CAD.0000000000001782","DOIUrl":"10.1097/CAD.0000000000001782","url":null,"abstract":"<p><p>This study compared the efficacy and safety of S-1 + oxaliplatin (SOX) plus sintilimab, albumin-bound paclitaxel + oxaliplatin (P-SOX), and docetaxel + oxaliplatin + 5-fluorouracil (DOF) as neoadjuvant regimens for advanced gastric cancer. We retrospectively analyzed 289 patients who received neoadjuvant and adjuvant chemotherapy followed by standard D2 radical gastrectomy (SOX + sintilimab, n  = 81; P-SOX, n  = 128; DOF, n  = 80). Patients were randomly divided 7 : 3 into training and validation sets. Short-term efficacy, long-term outcomes, and adverse events were evaluated, and predictors of progression-free survival (PFS) were explored. The objective response rate of SOX + sintilimab was 91.36% by tumor regression grade (TRG) and 70.37% by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), numerically higher than P-SOX (88.38 and 59.20%) and DOF (86.25 and 57.50%) without significance (TRG, P  = 0.587; RECIST 1.1, P  = 0.178). Median overall survival (OS) was 32 months [95% confidence interval (CI): 30.00-not reached] with SOX + sintilimab, superior to P-SOX (28 months; 95% CI: 26.00-31.00) and DOF (26 months; 95% CI: 23.00- 32.00) ( P  = 0.007). Median PFS was 30 months (95% CI: 27.00-33.00) for SOX + sintilimab, 25 months (95% CI: 22.00-26.00) for P-SOX, and 22.5 months (95% CI: 19.00-26.00) for DOF ( P  = 0.096). Common adverse events included grade 1-2 gastrointestinal reactions, peripheral neurotoxicity, and alopecia, with good tolerability. SOX plus sintilimab achieved the most favorable OS with comparable safety.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"253-264"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12955979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Initial stage analysis of tislelizumab in combination with chemotherapy for patients with advanced HIV-positive non-small-cell lung cancer: a comparative clinical trial.","authors":"Yaping Quan, Hao Li, Zhengjie Liang, Jie Shen, Yong Hu","doi":"10.1097/CAD.0000000000001784","DOIUrl":"10.1097/CAD.0000000000001784","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) are a standard treatment for advanced non-small-cell lung cancer (NSCLC), but limited data exist regarding their use in patients with HIV-positive. This study evaluated the efficacy and safety of ICI-based therapy in this population. In this single-center, comparative study, 18 patients with treatment-naive advanced NSCLC with HIV (experimental group) and 40 HIV-negative controls (control group) received 4-6 cycles of tislelizumab plus platinum-based chemotherapy, followed by tislelizumab maintenance until disease progression or unacceptable toxicity. A higher incidence of tuberculosis was observed in the experimental group compared with the control group (33.3 vs. 20.0%). The objective response rate was 77.8% [95% confidence interval (CI): 56.5-99.1] in the experimental group and 77.5% (95% CI: 64-91) in the control group ( P  = 0.981). The 6-month progression-free survival rate was 83.3% (95% CI: 64.3-99.9) for the experimental group and 82.5% (95% CI: 70.2-94.8) for the control group ( P  = 0.227). The 6-month overall survival rate was 88.9% (95% CI: 72.8-99.9) in the experimental group and 97.5% (95% CI: 92.4-99.9) in the control group ( P  = 0.192). The incidences of grade 3 or higher adverse events were 38.9 and 32.5% in the experimental and control groups, respectively. One patient in the experimental group died due to a serious opportunistic infection. Immunotherapy combined with chemotherapy showed comparable efficacy and safety in patients with advanced NSCLC irrespective of HIV status. Patients with HIV-positive had a higher tendency for opportunistic infections, including tuberculosis.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"272-279"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12955966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145429974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal treatment with thiotepa, bevacizumab, teniposide, and tunlametinib in a patient with neurofibromatosis type 1-associated oligodendroglioma: a rare case report.","authors":"Shizhen Zhou, Yanfei Chen, Guoliang Gao, Xueqiang Pan, Peng Sun, Rongjie Tao","doi":"10.1097/CAD.0000000000001786","DOIUrl":"10.1097/CAD.0000000000001786","url":null,"abstract":"<p><p>Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder associated with central nervous system gliomas, most frequently optic pathway gliomas; however, oligodendrogliomas in the setting of NF1 are exceedingly rare, with no prior documented cases and no established treatment strategies to date. A 53-year-old female with NF1-associated oligodendroglioma experienced multiple recurrences following surgery, radiotherapy, chemotherapy, and targeted therapy. Upon further disease progression, she was treated with a novel combination of thiotepa, bevacizumab, teniposide, and the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor tunlametinib. After one treatment cycle, the patient achieved a marked reduction in tumor volume, consistent with a complete response (CR). She subsequently completed eight additional cycles of the regimen and has maintained CR. The treatment was well-tolerated, with manageable grade 3 myelosuppression controlled by supportive care. As of June 2025, the patient has achieved a CR with a progression-free survival of 9 months before experiencing disease recurrence. This rare case of NF1-associated oligodendroglioma was managed with thiotepa, bevacizumab, teniposide, and tunlametinib, highlighting the potential of MEK inhibition in NF1-related gliomas.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"297-300"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145429956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel HEAT repeat protein 5B anaplastic lymphoma kinase fusion in lung adenocarcinoma confers sensitivity to ensartinib.","authors":"Guangyi Zhang, Di Wu, Haitao Deng, Qiuyun Xiao, Huiyun Peng","doi":"10.1097/CAD.0000000000001803","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001803","url":null,"abstract":"<p><p>Anaplastic lymphoma kinase (ALK) rearrangements are rare but highly actionable drivers in non-small cell lung cancer; however, uncommon fusion variants lack standard management. We report the clinical outcome of a novel HEAT repeat protein 5B (HEATR5B)-ALK fusion treated with ensartinib. A 52-year-old Chinese woman with stage IVA lung adenocarcinoma and left adrenal metastasis underwent tumor biopsy. Targeted DNA-based next-generation sequencing (NGS) identified HEATR5B(END..EX7)-ALK(IVS19..END) fusion; ALK protein expression was confirmed by immunohistochemistry (IHC). Ensartinib 225 mg orally once daily was initiated. Serial CT scans were evaluated according to RECIST 1.1; progression-free survival (PFS) and adverse events were recorded. The patient achieved a confirmed partial response at first restaging and maintained treatment for greater than 24 months without radiologic progression. No grade greater than or equal to 3 adverse events were observed; preexisting weight loss ceased. PFS is ongoing at the last follow-up (24+ months). The HEATR5B-ALK fusion is targetable by ensartinib, producing durable disease control and excellent tolerability. Comprehensive NGS and ALK IHC are essential for detecting rare actionable ALK variants.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-Aminoisoquinolines inhibit selectively phosphodiesterase 4B in KRAS-mutated colorectal cancer cell lines in-vitro and in-vivo.","authors":"Gennady B Lapa, Toshiyuki Tsunoda, Natalia I Moiseeva","doi":"10.1097/CAD.0000000000001819","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001819","url":null,"abstract":"<p><p>Phosphodiesterase 4B (PDE4B), an isoform of cyclic nucleotide phosphodiesterases, is integrated into cell membranes and hydrolyzes cyclic AMP in specific cellular compartments. Overexpression of PDE4B has been observed in hematological and gastrointestinal tumors harboring KRAS mutations, leading to the disruption of cell cycle regulation. Utilizing molecular docking, we identified 3-aminoisoquinolines as potential selective PDE4B inhibitors. Phenotypic screening on HKe3-KRAS cell lines confirmed that PDE4B is a selective target for these novel 3-aminoisoquinolines. We employed molecular docking and calculated ligand efficiency as predictive tools for methylthiazoltetrazolium assay activity to reduce the combinatorial library size. Six active compounds (047, 048, 086, 089, 091, and 099) were screened. Active compounds 047, 048, 086, 089, and 091 demonstrated selectivity toward HKe3-mtKRAS over wild-type cells. This 'synthetic lethality-like' approach was effective in predicting the anticancer properties of these compounds in KRAS-mutated cell lines. NCI-DTP 60 cell lines assays confirmed the activities of 047, 048, and 089. Compound 089 showed strong cytotoxicity against HCT-116 cells inhibitory concentration (IC50) = 1.6 μM, growth inhibition (GI50) = 0.53 μM, and an inhibitory concentration (IC50) against PDE4B = 2.5 μM. In addition, 089 exhibited good tolerability in a nude mouse HCT-116 xenograft model, but it was less effective at a dose of 40 mg/kg compared with Apremilast at a dose of 30 mg/kg in 8-s day's assay. While 089 had lower in-vivo efficacy than apremilast, its novel 3-aminoisoquinoline scaffold and high tolerability make it a superior candidate for further optimization.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: successful use of repotrectinib in a ROS1 fusion-positive lung adenocarcinoma patient with severe renal insufficiency and prior tyrosine kinase inhibitor treatment failure.","authors":"Zhengjie Liang, Hao Li","doi":"10.1097/CAD.0000000000001818","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001818","url":null,"abstract":"<p><p>During sequential targeted therapy for ROS1 fusion-positive non-small cell lung cancer, some patients may develop severe renal insufficiency due to drug-related adverse events, resulting in limited subsequent treatment options with uncertain efficacy. We report a case of a 69-year-old female patient with advanced lung adenocarcinoma harboring an SDC4-ROS1 fusion mutation. Imaging revealed multiple nodules and masses in both lungs, enlarged mediastinal lymph nodes, and bilateral pleural effusion. The patient received treatment with crizotinib and entrectinib successively. During this period, the patient experienced renal hemorrhage and developed renal cysts and renal atrophy. Laboratory findings revealed persistently elevated serum creatinine levels and a significant decline in estimated glomerular filtration rate. She ultimately developed severe renal insufficiency, concurrent with tumor progression. Repotrectinib therapy was initiated based on tumor progression and renal function status under close monitoring, and an objective response occurred in this patient. Moreover, the serum creatinine levels decreased and remained relatively stable, indicating improved renal function. No new severe drug-related adverse events were observed. This case suggests that in patients with ROS1 fusion-positive nonsmall cell lung cancer who have experienced prior ROS1-tyrosine kinase inhibitor treatment failure and concomitant severe renal insufficiency, repotrectinib may represent a potential and tolerable treatment option when fully assessing clinical risks and ensuring close monitoring.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D430-2307 inhibits breast cancer cell growth by dual induction of apoptosis and G0/G1 arrest via phosphatidylinositol 3-kinase/protein kinase B signaling.","authors":"Jingge Xu, Shuling Ni, Yi Yang, Deqiao Sheng, Yayun Liu","doi":"10.1097/CAD.0000000000001817","DOIUrl":"10.1097/CAD.0000000000001817","url":null,"abstract":"<p><p>D430-2307 is a novel small-molecule compound identified through virtual screening of the Chemdiv database that markedly inhibited the proliferation of both MCF-7 and MDA-MB-231 breast cancer cells. In the present study, the anticancer activity and underlying molecular mechanisms of D430-2307 were investigated. Thiazolyl blue, colony formation, wound healing, and transwell assays were performed to assess the effects of D430-2307 on breast cancer cell proliferation, migration, and invasion. To elucidate the underlying mechanisms, flow cytometry, Western blotting, and fluorescence staining were performed to analyze cell-cycle distribution, apoptosis, and intracellular reactive oxygen species (ROS) levels. In addition, network pharmacology, transcriptomics, and bioinformatics analyses were integrated to identify core targets and associated pathways, while molecular docking was performed to verify target-ligand interactions. The results demonstrated that D430-2307 significantly inhibited breast cancer cell proliferation, migration and invasion, induced G 0 /G 1 cell cycle arrest, downregulated CDK4/6 expression, and promoted apoptosis through modulation of the Bax/Bcl-2 ratio and activation of caspase-3/7 signaling. Furthermore, D430-2307 suppressed the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway via elevation of intracellular ROS levels. These findings suggest that D430-2307 exerts antitumor effects through ROS-mediated suppression of PI3K/AKT signaling, G 0 /G 1 cell cycle arrest, and apoptosis induction, providing a foundation for the development of novel anti-breast cancer therapeutics.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Envafolimab combined with chemotherapy in advanced thymic carcinoma - first clinical experience with a novel subcutaneous programmed death-ligand 1 inhibitor.","authors":"Wenju Sun, Haitao Wan","doi":"10.1097/CAD.0000000000001805","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001805","url":null,"abstract":"<p><p>Thymic carcinoma is rare with poor prognosis, and novel treatments are needed. We report two cases of advanced thymic carcinoma treated with the programmed death-ligand 1 inhibitor envafolimab with chemotherapy (liposomal paclitaxel and cisplatin). Case 1: A 59-year-old woman with metastatic thymic carcinoma (suspected neuroendocrine carcinoma) involving liver and bone received radiotherapy for spinal metastasis followed by eight cycles of envafolimab with liposomal paclitaxel and cisplatin. She achieved a partial tumor response with lesion shrinkage and normalization of liver function and tumor markers without grade 3 or higher adverse events, but later developed disease progression with anterior mediastinal mass enlargement, new left lung metastasis, bilateral pleural effusion, ascites, and pelvic effusion. Because of rapid disease progression and intolerance to further antitumor therapy, the patient died in May 2025. Her progression-free survival (PFS) was 6 months and overall survival was 10 months. Case 2: A 69-year-old man with metastatic thymic squamous carcinoma and multiple comorbidities was treated with definitive radiotherapy to the mediastinal tumor and eight cycles of envafolimab with chemotherapy. He achieved a complete response with tumor reduction and normalized markers. Treatment was well-tolerated without grade 3 or higher adverse events. As of the latest follow-up, PFS was 9 months, and he continues maintenance envafolimab with good tolerance. Both patients achieved PFS (6 and 9 months, respectively) that exceeded the median PFS reported in previous clinical studies using chemotherapy alone (5 months). This combination warrants further investigation in clinical trials.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone lactylation promoted colorectal cancer progression by enhancing tumor necrosis factor transcription and served as a diagnostic biomarker.","authors":"Shiyang Li, Xiufang Shi, Xiaoyue Zhou","doi":"10.1097/CAD.0000000000001771","DOIUrl":"10.1097/CAD.0000000000001771","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, with unmet needs for early diagnostic biomarkers and therapeutic targets. Recent studies highlight the role of histone lactylation (H3K18la) in modulating gene expression and tumor progression. Its specific mechanisms in CRC, however, remain poorly understood. This study analyzed 60 CRC patients to evaluate H3K18la levels in tumor and adjacent nontumor tissues via Western blot and correlated them with clinical parameters. CRC cell lines were treated with sodium lactate (Nala) to investigate H3K18la's regulatory effects on tumor necrosis factor (TNF) transcription. Mechanistic insights were derived from RNA sequencing, chromatin immunoprecipitation (ChIP) assays, luciferase reporter assays, and RT-qPCR. Diagnostic potential was assessed using receiver operating characteristic curve analysis. H3K18la levels were significantly elevated in CRC tissues compared with adjacent tissues and exhibited high diagnostic accuracy. High H3K18la expression correlated with larger tumor size and advanced american joint committee on cancer (AJCC) stages. Furthermore, H3K18la levels positively correlated with serum carcinoembryonic antigen and carbohydrate antigen 19-9. Nala treatment enhanced H3K18la enrichment at the TNF promoter, upregulating TNF transcription in CRC cells. Mechanistically, H3K18la directly activated TNF promoter activity, as demonstrated by luciferase reporter assays and ChIP analysis. In conclusion, H3K18la serves as a promising diagnostic biomarker for CRC, with strong correlations to tumor progression. Its oncogenic role is mediated, at least partially, through transcriptional activation of TNF. These findings position H3K18la as a novel therapeutic target for CRC and underscore its potential for early detection and personalized treatment strategies.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"245-251"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}