Anti-Cancer Drugs最新文献

{"title":"Temozolomide-based therapy may remodel the tumor microenvironment and enhance immunotherapy sensitivity in advanced leiomyosarcoma.","authors":"Huijing Tan, Zhuo Li, Jianguo Zhou, Susheng Shi, Liming Jiang, Lijie Zuo, Aijiang Su, Huike Wang, Yuting Sun, Wenjuan Xuan, Yihebali Chi","doi":"10.1097/CAD.0000000000001826","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001826","url":null,"abstract":"<p><p>Leiomyosarcoma (LMS) is characterized by inherent resistance to immune checkpoint blockade, with no conclusive evidence supporting the efficacy of programmed death-1 (PD-1)/programmed death-ligand 1 inhibitor, and it is generally classified as a nonimmunogenic sarcoma subtype. This study analyzed the therapeutic efficacy of temozolomide (TEM)-based regimens in patients with advanced LMS and evaluated pathological changes after TEM treatment to explore the potential role of immunotherapies and the mechanisms that could enhance immunotherapy sensitivity after TEM treatment. This retrospective review included patients with advanced LMS treated at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. All patients initiated TEM-based treatments between September 2018 and December 2024. We evaluated patients with advanced LMS and available pathological data before and after TEM-based therapy and those who received subsequent immunotherapy. In total, 47 patients received anthracycline combined with TEM, and 18 patients received gemcitabine combined with TEM. Overall median progression-free survival (mPFS) was 10.0 months, whereas median overall survival (mOS) was 31.0 months. Among six patients who received subsequent PD-1-based immunotherapy after TEM-containing regimens, mPFS and mOS were 13.0 and 45.0 months, respectively. O6-methylguanine DNA methyltransferase negativity tended to be associated with improved survival. Post-TEM biopsies revealed dynamic changes in mismatch repair gene expression, tertiary lymphoid structure counts, and the combined positive score. TEM-based regimens are effective for advanced LMS. Furthermore, pathological changes observed after TEM treatment suggest potential modulation of the tumor microenvironment, supporting further investigation into the integration of immunotherapies in this setting.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809740","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":"Locoregional and symptomatic response to neoadjuvant dual HER2 blockade with chemotherapy in HER2-positive breast cancer: a pilot study.","authors":"Gurjeet Singh Chowdhary, Ankush Nayyar, Sridharan Vasudevan, Kamalpreet Kaur","doi":"10.1097/CAD.0000000000001780","DOIUrl":"10.1097/CAD.0000000000001780","url":null,"abstract":"<p><p>Dual HER2 blockade with trastuzumab and pertuzumab in combination with chemotherapy has improved pathological complete response (pCR) rates in HER2-positive breast cancer in randomized trials. However, real-world pilot data on locoregional and symptomatic outcomes in patients receiving this regimen before surgery are limited. This was a prospective pilot study including 20 patients with HER2-positive breast cancer treated with neoadjuvant trastuzumab, pertuzumab, and chemotherapy. Patients were assessed clinically and radiologically at baseline and following completion of neoadjuvant therapy. Primary endpoints were locoregional response (tumor shrinkage, nodal downstaging, and operability) and symptomatic improvement (pain, heaviness, and nipple/skin changes). All patients subsequently underwent definitive surgery. Median age was 46 years (range 32-65). Most patients presented with locally advanced disease, and 70% had palpable axillary nodes. Following neoadjuvant therapy, the overall clinical response rate was 85%, with 25% achieving complete clinical response and 60% partial response. Median tumor reduction was approximately 50%. Nodal downstaging was seen in 60%, with complete nodal response in 30%. Symptomatic improvement was reported in 80% for pain, 70% for heaviness, and 60% for skin/nipple changes. All patients proceeded to surgery, and pCR was achieved in 25%. The regimen was well tolerated, with no major cardiac events or treatment-related mortality. Neoadjuvant dual HER2 blockade with chemotherapy is feasible in HER2-positive breast cancer, achieving high clinical response rates, meaningful symptomatic improvement, and acceptable safety in this pilot study. These findings provide early single-center, prospective pilot evidence supporting dual HER2-targeted neoadjuvant therapy, with implications for operability and patient-centered outcomes. Larger multicentre studies are needed to validate these results.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"265-271"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145429954","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":"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":2.0,"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":2.0,"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":2.0,"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":"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}

{"title":"Collagen I is the effective therapeutic target for treating desmoid tumors.","authors":"Yehyeong Lee, Yonghyo Kim, Chankyoung Lee, Tae Il Kim, Yong-Hee Cho","doi":"10.1097/CAD.0000000000001781","DOIUrl":"10.1097/CAD.0000000000001781","url":null,"abstract":"<p><p>Desmoid tumors, known as aggressive fibromatosis, are derived from connective tissues, and local invasion is usually observed. Despite intensive efforts have been performed to investigate the novel anticancer agents in desmoid tumors, effective clinical management for treating desmoid tumors has not been developed yet. Additionally, the molecular mechanisms involved in the tumorigenesis of desmoid tumors have not been elucidated. In this study, given the frequent mutations of Wnt components and loss of function mutations in Trp53 in desmoid tumors, we developed the mouse models harboring Apc mutation with/without Trp53 knockout , Apc1638N/+ , and Apc1638N/+/Trp53-/- , respectively. We then established two primary cells derived from desmoid tumors in Apc1638N/+ and Apc1638N/+/Trp53-/- . Next, we have screened 3120 chemicals from a Food and Drug Administration-approved chemical library and identified halofuginone hydrobromide (HH), a collagen I-targeting compound, as exhibiting the most significant growth inhibition effects on Apc1638N/+ and Apc1638N/+/Trp53-/- desmoid tumor cells. Notably, HH also showed dramatic anticancer effects on colorectal cancer cells and mouse tumor organoids derived from intestinal tumors ( Apc1638N/+ ). Taken together, targeting collagen I is an effective therapeutic strategy for treating desmoid tumors and colorectal cancer patients.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"181-189"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437094","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":"Identification of uridine phosphatase 1 as a potential therapeutic target in gastric cancer by integrated bioinformatics analysis and experimental validation.","authors":"Yongfeng Wang, Yichen Feng, Chengzhang Zhu, Ling Guan, Shengfeng Wang, Anqi Zou, Miao Yu, Yuan Yuan, Hui Cai","doi":"10.1097/CAD.0000000000001745","DOIUrl":"10.1097/CAD.0000000000001745","url":null,"abstract":"<p><p>Gastric cancer remains a major global health challenge, and its early diagnosis and prognosis prediction pose significant challenges to the current clinical treatment of gastric cancer. Finding gastric cancer biomarkers is essential to comprehending its pathophysiology and creating novel targeted treatments. Following the acquisition and processing of the gastric cancer sample, the single-cell RNA sequencing data, monocyte subpopulation characterization, and cell type identification were performed. Key gene modules linked to gastric-cancer-related monocytes were identified using high-dimensional weighted gene co-expression network analysis. Machine-learning diagnostic models were created utilizing the discovered gastric-cancer-related monocyte-related genes (GCRMORGs). A prognostic model was developed with the uridine phosphatase 1 ( UPP1 )-related risk scores and verified in separate cohorts, and multiple immunological analyses were performed. Finally, using various experimental assays, we thoroughly investigated the function of the UPP1 gene in gastric cancer. Gastric cancer samples showed a distinct immune milieu topography with an abundance of monocytes. Eventually, 32 GCRMORGs were identified. Diagnostic models demonstrated a high degree of efficacy in differentiating between patients with gastric cancer and the control group. The prognostic model showed significant predictive value for gastric cancer patients' survival. At the same time, we have confirmed from experimental perspectives that a poor prognosis for patients is indicated by a high expression of UPP1 in gastric cancer tissue. Important monocyte subpopulations associated with gastric cancer samples were detected in our investigation. The prognosis of patients with gastric cancer can be predicted using a predictive model based on 32 GCRMORGs. In addition, focusing on UPP1 in gastric cancer may yield novel therapeutic targets and approaches.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"217-237"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939603","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}