BACKGROUND There are few drugs available for the third-line treatment of metastatic colorectal cancer (mCRC), and efficacy is generally poor. Fruquintinib, an anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor, has been approved for mCRC; however, its efficacy as a single agent is not satisfactory. Most patients with mCRC are microsatellite stable (MSS), and not sensitive to immunotherapy. The combination of fruquintinib and immunotherapy may improve the survival of patients with mCRC. AIM To report the real-world experience using this combination therapy for MSS mCRC in routine clinical practice. METHODS The medical records of six patients with MSS mCRC who received third-line treatment with fruquintinib plus sintilimab between January 2022 and June 2024 were retrospectively reviewed. Survival analysis was performed using the Kaplan-Meier method. RESULTS One patient achieved a complete response, one had stable disease, and four experienced progressive disease. Median progression-free survival was 3.8 months, and median overall survival was 5.7 months. Common adverse reactions included bone marrow suppression, liver function impairment, and hypothyroidism, predominantly grades 1-2, with no grade 4 adverse reactions reported. CONCLUSION Our single-center experience in a small cohort implies fruquintinib combined with sintilimab may be efficacious and safe for select patients in the third-line treatment of mCRC. This combination therapy warrants further exploration.

Chronic obstructive pulmonary disease (COPD) is a globally burdensome chronic disease. Traditional symptomatic treatments cannot halt progressive lung function decline, making remodeling the diseased pulmonary microenvironment a core focus of disease-modifying therapy. COPD pathology involves uncontrolled airway inflammation, remodeling, and alveolar destruction, along with systemic immune, metabolic, and microbiome dysregulation. Molecular studies have revealed that cross-regulatory signaling, epigenetic reprogramming, metabolic remodeling, and immune dysfunction drive progression. Despite biomarker-guided stratification, current therapies remain homogeneous and lack target specificity. Emerging strategies focus on microenvironmental modulation, including immune-targeted therapy, antioxidant/anti-fibrotic interventions, cell/gene therapy, microbiome regulation, and advanced drug delivery systems to overcome the barriers for improved therapeutic efficacy. Digital and personalized optimization of inhalers further enhances precision. Multidisciplinary integration will accelerate clinical translation. This shifts the paradigm from passive symptom management to active microenvironment remodeling. This approach represents a promising strategy to slow COPD progression and improve outcomes.

The oncogenic role of RUNX1 in epithelial tumors is increasingly recognized, however, its function and mechanism within the tumor immune microenvironment (TME) of colorectal cancer (CRC) remain unclear. This study investigates the contribution of RUNX1 to TME remodeling in CRC. Analysis of clinical CRC tissues revealed that RUNX1 expression is negatively correlated with GITRL levels in tumor cells and is associated with increased infiltration of Treg cells. Functional studies demonstrated that RUNX1 impairs GITRL-GITR signaling, thereby promoting Treg cell infiltration while suppressing CD8+ T cell activation. Consequently, elevated RUNX1 expression enhanced the sensitivity of CRC tumors to GITR agonistic antibody therapy in a C57BL/6J mouse model. Mechanistically, RUNX1 interacts with STAT1 to inhibit its dimerization and subsequent transcriptional activation of GITRL, thereby suppressing GITRL expression. Our findings highlight the RUNX1/STAT1/GITRL axis as a potential therapeutic target for GITR-based immunotherapy in CRC.

Fasting-mimicking diets (FMD) have been reported to increase the anti-tumor efficacy in preclinical studies in various cancers. FMD can impact the tumor microenvironment (TME), and elucidating the mechanisms and cells mediating the effects of FMD may uncover combination treatment strategies. Here, we performed single-cell transcriptomic sequencing to characterize the TME changes induced by FMD intervention in a mouse model of spontaneous breast cancer. The sequencing data indicated that FMD suppressed tumor cell stemness, promoted apoptosis, and increased the infiltration of innate and adaptive immune cells, especially natural killer (NK) cells and effector CD8+T cells. Importantly, FMD induced phenotypic reprogramming of cancer-associated fibroblasts (CAFs), leading to a decrease in the immunosuppressive inflammatory CAF (iCAF) subset. Mechanistically, FMD decreased platelet-derived growth factor C (PDGFC) secretion in tumor cells by reducing glucose and inhibiting glycolysis to reprogram CAFs. PDGFC increased activation of the JAK/STAT3 pathway, which induced iCAF differentiation. Combining FMD with PDGFR inhibitors increased the efficacy of anti-PD-L1 immunotherapy in vivo. Overall, this study reveals a mechanism of metabolic-immune rewiring through which FMD suppresses tumor progression, providing preliminary evidence for the potential of combination FMD-based strategies in breast cancer treatment.

Background/Objectives: Biallelic mutations of NLRP7, a maternal-effect gene encoding a key component of the subcortical maternal complex, are the major monogenic cause of recurrent hydatidiform mole (RHM) and confer a substantial lifetime risk of gestational trophoblastic neoplasia (GTN), including choriocarcinoma. Although oocyte donation is currently the standard reproductive option, anecdotal live births from autologous oocytes in carriers of specific missense variants raise mechanistic and clinical questions that have not been integrated. We aimed to synthesize the current understanding of NLRP7 biology, oncogenic mechanisms in GTN, and genotype-stratified reproductive outcomes, and to propose a genetic permissiveness framework that links cancer surveillance with reproductive decision-making. We also place this monogenic disease in an epidemiological context, given the marked geographical variation in molar pregnancy incidence. Methods: PubMed, Embase and Web of Science were searched from January 2006 to December 2025 using terms related to NLRP7, hydatidiform mole, GTN, choriocarcinoma, maternal-effect genes, genomic imprinting, and assisted reproduction. Original studies, case series, expert consensus statements, and reviews were included. Results: NLRP7 loss disrupts subcortical maternal complex assembly, maternal-DMR methylation, trophoblast differentiation, and HLA-C-dependent immune privilege; in choriocarcinoma, NLRP7 is conversely reported to be up-regulated, where it has been implicated in tumor proliferation and immune evasion through inflammasome-independent pathways. Genetic permissiveness for autologous-oocyte pregnancy is mutation-type dependent: complete loss-of-function variants confer near-zero permissiveness, whereas missense variants with retained partial function may permit rare normal pregnancies. Conclusions: A genetic-permissiveness framework integrating variant-level functional data, GTN risk, and reproductive priorities can support shared decision-making in this rare but high-stakes clinical scenario, and it identifies clear directions for future translational research. We emphasize, however, that this framework has not been prospectively validated and should be regarded as hypothesis-generating rather than as a clinically established decision-making model. Recognizing the biallelic NLRP7 mutation as a heritable cancer-predisposition state further supports genotype-informed, risk-stratified oncological surveillance.

Cancer metastasis is the leading cause of mortality associated with cancer, and the prognosis for patients diagnosed with colorectal cancer(CRC) largely depends on the occurrence of metastasis during the progression of the disease. A comprehensive understanding of the mechanisms underlying metastasis in CRC is essential for advancing treatment strategies. Through integrated bioinformatics analysis of mRNA expression profiles and epigenetic modifiers, we identified SMYD3 as the top differentially expressed histone modifier in CRC. Clinically, SMYD3 overexpression significantly associates with poor prognosis and enhances metastatic potential. Utilizing immunoprecipitation-mass spectrometry, we discovered RACK1 as a novel SMYD3-interacting protein. Subsequent mechanistic studies revealed a tripartite interaction network: SMYD3 recruits SMAD3 through RACK1-mediated scaffolding, facilitating transcriptional activation of the downstream effector TSKU. Notably, RACK1 depletion disrupts SMYD3-SMAD3 complex formation, establishing the critical role of this axis in metastasis regulation. Consequently, inhibiting the SMYD3-SMAD3 interaction may represent a promising therapeutic strategy for addressing CRC metastasis. In conclusion, targeting the SMYD3-RACK1-SMAD3 transcriptional complex presents a viable approach for the treatment of CRC metastasis.

PURPOSE:The neoCARHP aimed to investigate the efficacy and safety of investigator-selected taxane (docetaxel, paclitaxel, or nab-paclitaxel) plus trastuzumab and pertuzumab, with carboplatin (TCbHP) or without carboplatin (THP), in stage II and III human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS:The neoCARHP was a multicenter, randomized, phase III, noninferiority study. Eligible patients were women age 18 years or older with previously untreated, stage II and III, HER2-positive invasive breast cancer. Patients were randomly assigned (1:1) to receive six 3-week cycles of TCbHP or THP. The primary end point was pathologic complete response (pCR) rate in the breast and axilla (ypT0/is ypN0) in the modified intention-to-treat (mITT) population (all randomly assigned patients receiving at least one dose of study treatment). Safety was evaluated in all patients who received any study treatment. RESULTS:Between April 30, 2021, and August 27, 2024, 774 patients were randomly assigned and 766 were included in the mITT population (382 in THP and 384 in TCbHP). pCR was achieved in 245 (64.1% [95% CI, 59.1 to 69.0]) patients in the THP group and 253 (65.9% [60.9-70.6]) in the TCbHP group (absolute difference, -1.8% [95% CI, -8.5 to 5.0]; odds ratio, 0.93 [95% CI, 0.69 to 1.25]; Pnoninferiority = .0089). The THP group had fewer grade 3 and 4 adverse events (20.7% v 34.6%) and serious adverse events (1.3% v 4.7%) than the TCbHP group. The most common grade 3 and 4 adverse events with THP were neutropenia (6.8% v 16.4% with TCbHP), leukopenia (5.5% v 14.8%), and diarrhea (2.6% v 4.2%). No treatment-associated deaths occurred. CONCLUSION:THP provided noninferior pCR rates and improved tolerability compared with TCbHP. Omitting carboplatin may be applicable in HER2-positive breast cancer.

PURPOSE:Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached. Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. METHODS:We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. RESULTS:The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250-0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080-0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020-10.037; p = 0.046). CONCLUSION:There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Triple-negative breast cancer (TNBC) is commonly characterized by high-grade and aggressive features, resulting in an augmented likelihood of distant metastasis and inferior prognosis for patients. Tumor immune microenvironment (TME) has been recently considered to be tightly correlated with tumor progression and immunotherapy response. However, the actual heterogenous TME within TNBC remains more explorations. The thorough analyses of different cell types within TME were conducted on the self-tested single-cell RNA sequencing dataset which contained nine TNBC treatment-naïve patients, including subclusters classification, CellChat algorithm, transcription factors (TFs) expression, pseudotime analysis and functional enrichment assay. The malignant epithelial cluster was confirmed by copy number variations analysis, and subsequently LASSO-Cox regression was carried out to establish a Malignant Cell Index (MCI) model on the basis of five crucial genes (BGN, SDC1, IMPDH2, SPINT1, and UQCRFS1), which was validated in several TNBC cohorts through Kaplan–Meier survival and immunotherapy response analyses. The public spatial transcriptome, proteome data and qRT-PCR, western blotting experiments were exploited to corroborate UQCRFS1 expression in RNA and protein levels. Additionally, functional experiments were implemented to unravel the impacts of UQCRFS1 on TNBC cells. The diverse subclusters of TME cells within TNBC were clarified to display distinct characteristics in cell–cell interactions, TFs expression, differentiation trajectory and functional pathways. Particularly, IL32high Treg imparted an essential effect on tumor evasion and predicted a worsened prognosis of TNBC patients. Furthermore, MCI model enabled to notify the inferior prognosis and immunotherapy resistance in TNBC. Ultimately, UQCRFS1 knockdown dampened the proliferative and migratory competence in vitro as well as tumor growth in vivo of TNBC cells. Our study offers innovative perspectives on comprehending the heterogeneity within TME of TNBC, thereby facilitating the elucidation of TNBC biology and providing clinical recommendations for TNBC patients' prognosis, such as IL32high Treg infiltration, MCI evaluation, and UQCRFS1 expression.

The study aimed to identify the prognostic factors affecting survival among patients with duodenal adenocarcinoma (DAC) and isolated hepatic metastases (HM). We conducted a retrospective analysis of clinical data from 51 patients treated for DAC and HM from January 2012 to January 2018. The Kaplan–Meier method and log-rank test were used for survival analysis. The Cox proportional hazards regression model was utilized for multivariate analysis. Thirty-nine patients had synchronous HM, and 12 patients exhibited metachronous HM. Median overall survival (mOS) for patients with synchronous HM was 6.8 months, versus 45.9 months for those with metachronous HM (P < 0.001). mOS for the patients who received first-line chemotherapy was 18.9 months, compared with 4.4 months for the patients who did not undergo first-line chemotherapy (P < 0.001). Multivariate analysis identified the timing of HM detection and the receipt of first-line chemotherapy as independent prognostic factors. Subgroup analysis revealed that among patients with synchronous HM, mOS for patients who underwent primary tumor resection was 16.9 months, compared with 3.5 months for those who did not undergo resection (P < 0.001). The timing of detection of HM and the receipt of first-line chemotherapy are independent prognostic factors for patients with DAC and isolated HM.

Neoadjuvant therapies are essential for managing high-risk early-stage breast cancer, but their effectiveness is limited, necessitating the exploration of the optimal neoadjuvant treatment strategy based on innovative subtypes. Given the heterogeneity inherent in breast cancer, there is growing need for identifying novel molecular subtypes predictive of treatment response through multi-omic analyses. A comprehensive analysis was performed using data from 142 high-risk early breast cancer patients, including genomic, transcriptomic, proteomic, and phosphoproteomic profiles. The molecular subtypes were explored based on the biological characteristics and responses to neoadjuvant treatments. The results were also validated in the TCGA-breast cancer cohort and external dataset. Three molecular subtypes were identified, each associated with different optimal treatment strategies. The immune-activated (IA) subtype displayed a significantly higher pathologic complete response (pCR) rate when treated with platinum-based neoadjuvant regimens, and exhibited heightened immune cell infiltration. The vesicular transport pathway-activated (VT) subtype, characterized by vesicular transport pathway activation, showed a favorable pCR rate to anthracycline-based neoadjuvant chemotherapy. In contrast, the kinase activation (KA) subtype demonstrated limited responsiveness to both platinum and anthracycline-based treatments and featured enrichment in non-canonical TGF-β signaling, MAPK/ATM kinase activation, and angiogenic signatures. A seven-gene classifier linked to non-canonical TGF-β signaling was created to identify the KA subtype, achieving an area under the curve value of 90

Objective To observe the expression levels of base excision repair(BER)pathway-related proteins in small cell lung cancer(SCLC)tissues,and analyze their relationship with the prognosis and tumor immune microenvironment.Methods A retrospective cohort study was conducted on 74 patients with limited-stage SCLC undergoing surgical treatment in our medical center from December 2018 to June 2023.Immunohistochemical staining was performed to analyze the protein expression of BER pathway components,apurinic/apyrimidinic endonuclease 1(APE1),8-oxoguanine DNA glycosylase 1(OGG1),DNA polymerase β(POLβ),X-ray repair cross-complementing protein 1(XRCC1),ATP-dependent DNA ligase I(LIGⅠ),and immune cell infiltration markers of CD3⁺ T cells,CD8⁺ T cells,CD68⁺ macrophages in SCLC tissues.Chi-square test was applied to analyze the relationship of BER protein expression and clinicopathological features;Kaplan-Meier survival curve was plotted to evaluate the impacts of BER protein expression and immune cells on disease-free survival(DFS)and overall survival(OS),multivariate Cox regression analysis was utilized to identify DFS prognostic factors,and Spearman correlation analysis was performed to analyze the correlation of BER-immune cell infiltration.In in vitro experiments,transient transfection was applied in H196 cells to overexpress APE1/POLβ/LIGⅠ,respectively.Thus,the cells were divided into negative control(NC,empty vector)and overexpression(OE,target plasmids)groups.CCK-8 and TUNEL assays were employed to determine the effects of OEAPE1,OEPOLβ and OELIGⅠon cell sensitivity to cisplatin.In in vivo experiments,nude mice bearing xenograft tumors were grouped into WT,E3330(APE1 inhibitor),cisplatin,and cisplatin+E3330 groups to determine the effects of the combination therapy on tumor growth.Results There were no significant correlations of the expression levels of key BER pathway proteins with clinicopathological characteristics,including gender,age,smoking history,tumor location,Ki67 index,or TNM stage(all P>0.05).The patients with low expression of APE1,POLβ,and LIGⅠ had obviously higher DFS rates than those with high expression(P<0.05),and the patients with larger proportion of CD3+T cells also had higher DFS rates than those with smaller proportion(P=0.043).Multivariate Cox regression analysis indicated that tumor TNM stage(HR=2.465)and APE1 expression(HR=2.730)were independent risk factors for the prognosis of SCLC patients(P<0.05).Spearman correlation analysis demonstrated a positive correlation between APE1 and CD8+T cell proportion in the SCLC patients(r=0.27,P<0.05).In vitro experiments showed that the overexpression(OE)cells(OEAPE1 and OELIGⅠ)exhibited reduced sensitivity to cisplatin than the NC group(P<0.05).Animal experiments indicated that cisplatin+E3330 significant inhibited xenograft tumor growth,indicating enhanced therapeutic efficacy(P<0.01).Conclusion High expression of APE1,POLβ,and LIGⅠ in the BER pathway indicates poor prognosis and low DFS rate in SCLC patients.High expression of APE1 is positively correlated with CD8+T cells,and can be used as an auxiliary marker for SCLC immunotherapy.

Deubiquitinating enzymes (DUBs) are responsible for the removal of ubiquitin from substrates, thereby antagonizing ubiquitination and regulating a multitude of biological pathways including cell cycle progression, signal transduction, and transcriptional regulation. Ubiquitin Specific Protease-39 (USP39), a pivotal member of the ubiquitin-specific protease family, is intricately linked to innumerable pathophysiological processes. In this review, we first provide an overview of the specific structural domains and biological functions of USP39, with a particular focus on its role in DNA damage repair and RNA splicing processes. Then, we delineate the function of USP39 in maintaining epithelial morphology, resistance to viral infection, vascular remodeling, and pathological states. Moreover, we particularly focus on the aberrant expression of USP39 in various cancers and its effect on cancer markers, as well as on the regulatory role of USP39 in tumor progression. In conclusion, a comprehensive analysis of the structural domains and functional properties of USP39, a detailed investigation into its interaction mechanisms with diverse substrates, and the accelerated development of related inhibitors will provide a novel theoretical foundation for the treatment of numerous diseases, including tumors. Importantly, targeting USP39 may overcome resistance to checkpoint inhibitors, offering a promising approach to enhance cancer immunotherapy efficacy.

The clinical performance of targeted therapies for treating hepatocellular carcinoma (HCC) is significantly limited by the frequent emergence of drug resistance, ultimately resulting in therapeutic failure and poor prognosis. While the precise mechanisms underlying this resistance are not fully elucidated. Emerging evidence implicated that reactive oxygen species (ROS) homeostasis and ferroptosis, a unique form of programmed cell death, are closely associated with the development of drug resistance in cancer cells. In this study, we demonstrated that circRNA-SORE, a circRNA previously reported by our group, played a crucial role in mediating sorafenib resistance via regulating intracellular ROS levels and inhibiting ferroptosis. Mechanically, we identified that circRNA-SORE exerted its regulatory effects through modulating the level of UBQLN1. UBQLN1, via its STI domain, stabilized GPX4, a crucial antioxidant enzyme that protects against ferroptosis death. The stabilization of GPX4 promoted cancer cell survival under sorafenib-induced oxidative stress. In conclusion, this study revealed a novel circRNA-SORE/UBQLN1/GPX4 regulatory axis that mediated sorafenib resistance in HCC and also offered a promising therapeutic strategy to overcome drug resistance and improve clinical outcomes for patients with HCC.

Clear cell renal cell carcinoma (ccRCC) is a common and lethal urinary malignancy characterized by its resistance to apoptosis. Despite the emerging treatment options available for ccRCC, only a small proportion of patients achieve long-term survival benefits. Previous studies have demonstrated that inducing tumor cell senescence, followed by treatment using senolytics, represents a potential strategy for triggering tumor cell apoptosis. However, it remains unclear whether this strategy is suitable for the treatment of ccRCC. Using the whole-genome CRISPR screening database Dependency Map portal (DepMap), we identified ribonucleotide reductase family member 2 (RRM2), which catalyzes the conversion of ribonucleotides to deoxyribonucleotides (dNTPs), as an essential targetable gene for ccRCC. Herein, we report that the combination of the choleretic drug osalmid targeting RRM2 and the senolytic compound navitoclax targeting BCL-XL represents a novel therapeutic approach for ccRCC. Furthermore, we have validated this approach across a panel of human ccRCC cells with different genetic backgrounds and multiple preclinical models, including cell line-derived xenografts (CDX), patient-derived xenografts (PDX), and patient-derived organoids (PDO). Mechanistically, osalmid-mediated inhibition of dNTPs generation induces cellular senescence in ccRCC, concomitant with STAT3 activation and upregulation of BCL-XL, thus rendering these cells vulnerable to navitoclax, which targets the BCL-2 protein family.

BACKGROUND:Ovarian clear cell carcinoma (OCCC) is an aggressive epithelial ovarian cancer subtype that prevalent in East Asia. Competing endogenous RNA (ceRNA) networks involving circular RNAs (circRNAs) and microRNAs (miRNAs) represent underexplored regulatory layers in OCCC pathogenesis. METHODS:Multi-omics integration of circRNA (GSE271851 and GSE266248) and miRNA (GSE230956 and GSE200852) datasets from GEO was performed using DESeq2 and limma tools (|log2FC|≥1, p < 0.05). Experimentally validated circRNA-miRNA interactions were predicted using circBank 2.0, Circular RNA Interactome, and Starbase v3.0. ceRNA networks were constructed using inverse correlation principles and visualized in Cytoscape. Immune associations were assessed using TIMER2.0. Prognostic and expression validations were performed using the Kaplan-Meier Plotter and HPA databases, respectively. RESULTS:Three core circRNAs (hsa_circ_0002822, hsa_circ_0003641 and hsa_circ_0030509) were identified as being dysregulated across OCCC models. Their miRNA sponging activity formed a 65-node ceRNA network involving 15 miRNAs (e.g., miR-143-3p and miR-182-5p) and 47 mRNAs. Six targets (BRCA1, KRAS, MSH6, SMARCA4, SRC, and TSC1) exhibited significant correlations with immune infiltration (CD8+ T cells, Tregs, and MDSCs). High expression of BRCA1, KRAS, and MSH6 predicted poor survival, with protein-level upregulation confirmed in OCCC tissues. CONCLUSION:This study delineates a circRNA-driven ceRNA network in OCCC, and identifies BRCA1, KRAS, and MSH6 as multi-omic biomarkers with immune-modulatory roles. These findings provide a basis for the development of RNA-targeted therapies against this ovarian cancer subtype.

BACKGROUND:Treatment of metastatic gastric cancer (mGC) relies primarily on chemotherapy, which can be effectively combined with immunotherapy. Despite these interventions, overall survival remains suboptimal. CASE SUMMARY:We report a patient with mGC who received S-1 plus oxaliplatin with sintilimab as first-line therapy, followed by maintenance therapy with S-1 and sintilimab. After 6 months, a partial response was observed, with a 71.7% reduction in the target lesion. After 13 months, the reduction reached 76.3%. Treatment was temporarily paused for 6 months due to a pulmonary infection. Upon re-evaluation 6 months later, the tumor continued to regress, with a 79.4% reduction in the target lesion. The original regimen was then resumed. From diagnosis to date, progression-free survival has reached 23 months. CONCLUSION:Sintilimab combined with chemotherapy demonstrated improved progression-free survival and warrants further investigation in mGC.