Although targeted therapy has made significant advances in cancer treatment throughout these years, drug resistance still remains a major obstacle. Plenty of evidence has proved that abnormal expression of receptor tyrosine kinase AXL is associated with targeted therapy resistance and poor clinical outcomes. AXL drives drug resistance through diverse mechanisms, including altering tumor cell phenotypes, orchestrating DNA damage response process, promoting the activation of bypass signals, or interacting with other receptor tyrosine kinases. Preclinical and clinical studies have demonstrated that combined inhibition of AXL and the other target can enhance the efficacy of various targeted therapies and improve outcomes for patients with drug resistance. This review summarizes recent advances in the specific roles of AXL in targeted therapy resistance and AXL-targeted treatment strategies. It further explores the potential clinical value of combinatorial approaches involving AXL inhibition and discusses future directions for its application in developing novel targeted therapies and advancing precision oncology treatment. 
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Objective: To exploit the elevated glutathione (GSH) levels in the tumor microenvironment and investigate the therapeutic efficacy of a novel glutathione-responsive apurinic/apyrimidinic (AP) site captor, Probe-NEt, against anaplastic thyroid cancer (ATC). Methods: Fluorescence imaging compared Probe-NEt uptake and activation in normal thyroid (Nthy ori 3-1), ATC (THJ-16T, CAL-62), and lung cancer (H1299) cells. Half maximal inhibitory concentration (IC50) values were determined by cytotoxicity assays; DNA damage was evaluated using appropriate assays. Flow cytometry analyzed cell cycle distribution and apoptosis following treatment with low (5 μmol/L) or high (20 μmol/L) Probe-NEt concentrations. BALB/c nude mice bearing subcutaneous ATC xenografts received low (0.025 mg) or high (0.05 mg) dose injections. Tumor volumes were monitored; HE staining assessed biosafety in major organs; immunohistochemistry detected apoptosis-related protein expression. Results: ATC cells demonstrated significantly higher Probe-NEt activation than normal thyroid cells. Probe-NEt exhibited selective cytotoxicity (higher IC50 in normal vs. ATC cells; all P＜0.01) with time-dependent characteristics; the selectivity ratio increased from 1.7 at 24 h (62.4 vs. 37.7 μmol/L) to 2.4 at 48 h (32.7 vs. 13.5 μmol/L). Probe-NEt induced DNA damage, G2/M arrest (THJ-16T: from 5% to 43%; CAL-62: from 19% to 37%), and dose-dependent late apoptosis. In THJ-16T cells, late apoptotic rates rose from 5.49% (control) to 13.95% (low-dose) and 63.43% (high-dose), with viable cells decreasing accordingly (89.42%, 76.01%, 20.45%). CAL-62 cells showed similar trends (16.72%, 40.19%, 69.88%). In vivo, Probe-NEt significantly suppressed tumor growth without hepatorenal toxicity (all P＞0.167). Immunohistochemistry revealed upregulated pro-apoptotic proteins, downregulated anti-apoptotic proteins, and decreased Ki-67 expression. Conclusion: The glutathione-responsive AP site captor Probe-NEt significantly inhibits ATC cell growth, induces G2/M phase cell cycle arrest, promotes late apoptosis, and exhibits high selectivity and favorable biosafety profiles.

In recent years, antibody-drug conjugates (ADCs) have achieved remarkable progress in the treatment of solid tumors and are now widely applied in malignancies such as breast cancer, ovarian cancer, cervical cancer, urothelial carcinoma, and non-small cell lung cancer, demonstrating favorable clinical efficacy. However, with their expanding clinical use, safety challenges associated with ADCs have become increasingly apparent. Among these, ocular adverse events have received limited attention in the past but is now emerging as a clinically relevant concern, as it may impair patients' quality of life and necessitate treatment modifications. Due to differences in payloads, target specificity, and mechanisms of action, various ADCs may induce ocular adverse events, including corneal disorders such as dry eye and keratoconjunctivitis, which can lead to visual disturbances, diminished quality of life, and reduced treatment adherence. Consequently, appropriate preventive and management strategies are urgently needed in clinical practice. To address this gap, and based on the latest international and domestic clinical evidence as well as multidisciplinary expert experience in oncology and ophthalmology, a Chinese expert consensus was developed following extensive discussion. This consensus aims to enhance clinicians' awareness of ADC-associated ocular adverse events, promote the safe application of ADCs in the treatment of solid tumors, and ultimately improve patients' quality of life and therapeutic outcomes.

This study investigated the secondary metabolites of the endophytic fungus Penicillium sp. RM isolated from the toxic plant Rhododendron molle. Ten compounds were isolated and purified from the ethyl acetate extract of the fungal fermentation broth by silica gel column chromatography, gel column chromatography, and semi-preparative HPLC. The structures of these compounds were elucidated by comprehensive spectroscopic analyses, including NMR, MS, UV, IR, and CD. The identified compounds were as follows: penicidienone A(1), diversonol(2), alternariol(3), alternariol 9-methyl ether(4), methylated dechloromonilicin(5), norliquexantona(6), alternethanoxin A(7), α-diversonolic ester(8),(±)-asperlone A(9), and verruculotoxin(10). Compound 1 was identified as a new cyclopentenone derivative. Compound 9 showed inhibitory activity against the proliferation of HepG2(IC_(50)=9.7 μmol·L~(-1)), HGC27(IC_(50)=9.3 μmol·L~(-1)), and U251(IC_(50)=8.4 μmol·L~(-1)) cell lines.

Objective: To analyze the clinical characteristics of oral adverse reactions associated with novel anti-tumor drugs, providing references for early diagnosis and treatment to improve cancer patients' qualities of life and therapeutic efficacies. Methods: Clinical data and photographs of 11 tumor patients treated at Beijing Hospital from January 2020 to April 2025, who developed oral adverse reactions after receiving targeted therapy, antibody-drug conjugates (ADC), or immune checkpoint inhibitor (ICI), were collected. A retrospective analysis was conducted to summarize the clinical characteristics of these oral adverse reactions. Results: Among the 11 patients with oral adverse reactions related to novel anti-tumor drugs, 3 patients received targeted therapy alone, 1 patient received ADC alone, 1 patient received a combination of targeted therapy and ADC, and 6 patients were treated with ICI alone. The time from the first administration of the novel anti-tumor drug to the onset of oral adverse reactions ranged from 0.5 to 18.0 months. The clinical manifestations of oral adverse reactions were various, with oral mucositis (9 cases) being the most common, followed by xerostomia (7 cases), oral candidiasis (4 cases,), hemangioma (1 case), and exacerbation of a pre-existing condition (vitiligo, 1 case). Most adverse reactions were graded as level 2 (moderate), with one case at grade 1 (mild) and one case at grade 3 (severe). Five patients experienced concomitant cutaneous adverse reactions, including 1 patient on targeted therapy, 1 on combined targeted therapy and ADC, and 3 on ICI, presenting mainly as xerosis cutis, maculopapular rash, folliculitis-like rash, and paronychia. For the 10 patients with common terminology criteria for adverse events grade 2 or higher, local administration of corticosteroids and antifungal medications were provided. Severe cases received systemic medication along with comprehensive supportive treatment. Symptoms in all patients were alleviated. Conclusions: Novel anti-tumor drugs can induce diverse oral adverse reactions, necessitating early recognition and intervention by oncologists and dentists. Through enhanced multidisciplinary collaboration and medical education, combined with local and systemic therapies, patients outcomes and qualities of life can be effectively improved.

To evaluate the associations of serum methotrexate (MTX) concentrations and MTHFR gene polymorphisms with delayed metabolism of high-dose MTX and adverse reactions in children with acute lymphoblastic leukemia (ALL).

Bacterial outer membrane vesicles (OMVs) have attracted widespread attention in the field of drug delivery due to their excellent biocompatibility, tumor penetration, and loading capacity. The anti-angiogenic peptide AP25 can block malignant tumor angiogenesis and has broad-spectrum anti-cancer activity. To achieve efficient delivery of AP25, we modified AP25 on the surface of OMVs through genetic engineering and explored their inhibitory effects on breast cancer and gastric cancer in vitro. The results indicated that the engineered OMVs had typical morphological characteristics of OMVs, and the particle size distribution conformed to the theoretical. Proteinase K digestion combined with Western blotting confirmed that AP25 was modified on the membrane surface of OMVs. Cell experiments showed that WAP25 OMVs significantly inhibited the proliferation, migration, and invasion of MDA-MB-231 and HGC-27 cells, promoted the cell apoptosis, and downregulated the expression of tumor migration and angiogenesis-related proteins: integrin beta 1 (integrin β1), Homo sapiens inhibitor of DNA binding 1 (ID1), nuclear factor kappa-B (NF-κB), and vascular endothelial growth factor (VEGF). This study achieves effective delivery of protein drugs based on OMVs for the first time, providing new ideas for the anti-angiogenesis therapy for tumors and the functional development of bacterial OMVs.

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) is a crucial signaling network regulating cell proliferation, survival, and metabolism, which plays a central role in the pathogenesis and progression of breast cancer. Targeting the PAM pathway with inhibitors provides a novel precision therapeutic option for cancer patients. However, the broad suppression of physiological PAM pathway functions in normal tissues, combined with the distinct characteristics of their molecular targets, leads to both the uniqueness of adverse reactions associated with these agents and heterogeneity within their safety profiles. Given the complexity of the adverse reaction spectrum and the specialized management requirements for PAM pathway inhibitors, Cancer Drug Clinical Research Committee of China Anti-Cancer Association and Standard Construction Committee of China Anti-Cancer Association jointly convened a multidisciplinary expert panel to develop this consensus. This document systematically synthesizes epidemiological features, pathological mechanisms, and risk factors of PAM pathway inhibitor-associated adverse reactions. It provides clinicians with evidence-based guidance on standardized prevention strategies, early warning systems, assessment frameworks, intervention protocols, and long-term monitoring pathways. The ultimate goals are to maximize medication safety, optimize treatment adherence, and ultimately enhance antitumor efficacy and patient quality of life.

With the expanding use of immune checkpoint inhibitors (ICIs) in gastric cancer, surgical safety is facing new challenges. Perioperative immune-related adverse events (irAEs) can substantially overlap with postoperative complications in both time course and clinical presentation, increasing the risk of diagnostic confusion, missed or delayed recognition, and potentially fatal outcomes. Integrating evidence from prior studies and real-world clinical experience, this article focuses on perioperative irAEs in gastric cancer that are particularly prone to misclassification, such as ICI-related pneumonitis, hypophysitis, adrenal insufficiency, and hypothyroidism. We systematically summarize their epidemiology and common manifestations and, using a symptom-oriented approach, address typical perioperative scenarios including fatigue, hypotension, electrolyte disturbances, altered mental status, postoperative fever, hypoxemia, dyspnea, cough, and perioperative enzyme abnormalities. Practical diagnostic clues and management strategies are proposed to distinguish irAEs from surgical complications such as infection, hemorrhage, pulmonary complications, myocardial infarction, and surgery-related pancreatic injury. We further emphasize the need to establish a standardized, multidisciplinary team-based perioperative pathway in the era of neoadjuvant immunotherapy, incorporating comprehensive preoperative baseline assessment of cardiac, pulmonary, hepatic, and endocrine function; protocolized postoperative monitoring at key time points; and risk-stratified interventions. When irAEs are suspected, early specialist consultation and timely initiation of immunosuppressive therapy, particularly corticosteroids, are critical to reducing both diagnostic delay and unnecessary overtreatment, thereby maximizing the therapeutic benefit of immunotherapy while safeguarding surgical outcomes.

The widespread use of immune checkpoint inhibitors (ICIs) has led to breakthrough advances for patients with various advanced solid tumors. As the skin is an important target organ of immune responses, it is the most commonly affected site of treatment-related adverse events associated with ICIs, with a relatively high incidence of ICI-related skin toxicity events. Immune-related adverse events induced by ICIs are increasingly becoming a bottleneck limiting their clinical application. To collect post-marketing adverse events and medication errors related to drugs and therapeutic biological products and to evaluate real-world drug safety, the United States Food and Drug Administration (FDA) established the FDA Adverse Event Reporting System (FAERS) database. Based on the FAERS database, this study aims to systematically evaluate differences in the risk of skin toxicity events among different drug subtypes, cytotoxic-T-lymphocyte-associated antigen-4 inhibitors, programmed death-1 (PD-1) inhibitors, and programmed death-ligand 1 (PD-L1) inhibitors, and to explore the limitations and potential improvements of existing pharmacovigilance methods.

In recent years, immune checkpoint inhibitors (ICIs), as a revolutionary therapeutic approach in oncology, have demonstrated remarkable clinical efficacy across various malignant tumors. With the widespread clinical application of ICIs, their associated toxicities have emerged as a critical issue that urgently requires resolution in the field of cancer immunotherapy. ICIs-associated pneumonitis (CIP) specifically refers to immune-related adverse events (irAEs) of the lung induced by ICIs therapy, the underlying pathogenesis of which remains incompletely elucidated. As a rare yet severe complication of ICIs treatment, and CIP is characterized by insidious onset, rapid progression, poor prognosis, and high mortality rate, with highly heterogeneous clinical manifestations and radiological features. Due to the lack of specific biomarkers and objective diagnostic indicators, the early identification and diagnosis of CIP present significant clinical challenges. By reviewing previous literature and studies, this paper summarizes recent advances in understanding the clinical manifestations, risk factors, potential molecular mechanisms, biomarkers, and early warning systems of CIP in patients receiving immunotherapy for lung cancer. The aim of this article is to provide a reference for the clinical management of CIP and offer a theoretical basis for establishing an early screening and precision diagnosis and treatment system for this condition.
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To observe the clinical efficacy of heat-sensitive moxibustion in reducing toxicity and enhancing efficacy in cancer patients undergoing chemotherapy, and to provide a scientific basis for its application and promotion in cancer rehabilitation.

The aim is to investigate the ameliorative effects and underlying mechanisms of Fufang E'jiao Jiang on chemotherapy-associated muscle fatigue in 4T1 breast cancer-bearing mice. A cancer-related fatigue model was established by orthotopic injection of 4T1 cells to induce breast cancer, combined with intraperitoneal injection of paclitaxel. The efficacy of Fufang E'jiao Jiang in ameliorating breast cancer-associated muscle fatigue was evaluated through multimodal pharmacodynamic indices, including behavioral tests, biochemical analyses, and histopathological examinations. Untargeted metabolomics was employed to characterize the metabolic profiles and identify biomarkers in a 4T1 breast cancer-bearing mouse model with chemotherapy-associated muscle fatigue. Subsequently, targeted investigations were conducted to determine the effects of Fufang E'jiao Jiang on these metabolic profiles and biomarkers. Finally, the expression of key metabolic enzymes was detected by Western blot. Based on the tumor volume measurements, Fufang E'jiao Jiang did not exert a significant inhibitory effect on tumor volume. Behavioral results showed that Fufang E'jiao Jiang could increase the grip strength, swimming exhaustion time, rotarod residence time, treadmill exercise distance and exercise time of mice with muscle fatigue. Biochemical analysis revealed that Fufang E'jiao Jiang significantly downregulated the level of creatine kinase(CK) and lactate(LAC). Hematoxylin and eosin staining indicated that Fufang E'jiao Jiang increased the cross-sectional area of gastrocnemius muscle fibers. Transmission electron microscopy results showed that Fufang E'jiao Jiang significantly increased the length and width of gastrocnemius muscle fibers in fatigued mice, and restored mitochondrial morphology towards normal. Metabolomics identified 20 biomarkers in the gastrocnemius muscle of 4T1 breast cancer-bearing mice with chemotherapy-associated muscle fatigue. Fufang E'jiao Jiang significantly restored the level of 17 biomarkers, including L-arginine(Arg), L-aspartic acid(Asp), homocarnosine, and α-ketoglutarate(AKG). Furthermore, Fufang E'jiao Jiang upregulated metabolic pathways such as arginine biosynthesis, alanine-aspartate-glutamate metabolism, and arginine-proline metabolism. The Western blot results indicated that Fufang E'jiao Jiang participated in arginine biosynthesis and metabolism by upregulating argininosuccinate synthase 1(ASS1) activity and downregulating arginase 1(ARG1) activity. This study demonstrates that Fufang E'jiao Jiang significantly ameliorates chemotherapy-associated muscle fatigue in 4T1 breast cancer-bearing mice. The underlying mechanism may involve modulation of Arg biosynthesis and metabolic pathways to maintain systemic arginine homeostasis. These findings provide a preliminary foundation for elucidating the mechanism of Fufang E'jiao Jiang in managing breast cancer chemotherapy-related muscle fatigue.

This study aims to investigate the mechanism by which the n-butanol fraction of Wenxia Formula extract(NWXF) reverses cisplatin(DDP) resistance in lung cancer via targeting cancer-associated fibroblasts(CAFs)-mediated regulation of glutathione(GSH) synthesis. A combined in vivo and in vitro experimental approach was employed to examine the therapeutic effects and molecular mechanisms of NWXF in ameliorating DDP resistance: a subcutaneous tumor xenograft model in nude mice was established in vivo. The mice injected with non-small cell lung cancer cells(A549) were randomly divided into control group and DDP group, while those injected with A549+CAFs cells were divided into CAFs group, CAFs+DDP group, NWXF+CAFs group, and NWXF+CAFs+DDP group. Hematoxylin-eosin(HE) staining was utilized to observe tumor histomorphological changes. TUNEL staining and immunohistochemistry were employed to detect tumor apoptosis. DTNB assay was used to measure the GSH level, and Western blot was employed to detect expressions of glutamate-cysteine ligase catalytic subunit(GCLc), glutamate-cysteine ligase regulatory subunit(GCLm), and recombinant solute carrier family 7 member 11(SLC7A11) proteins. A conditioned co-culture model with A549 cells was constructed in vitro. Cell counting kit-8(CCK-8) assay was employed to detect A549 cell proliferation, and flow cytometry was used to measure apoptosis. DTNB was used to determine the levels of GSH and cysteine(Cys), and Western blot was utilized to examine the expressions of GCLc, GCLm, and SLC7A11 proteins. In vivo results demonstrated that compared to the CAFs+DDP group, the NWXF+CAFs+DDP group exhibited markedly reduced tumor volume, significant tumor necrosis, obviously increased apoptosis, and apparently downregulated GSH level and expressions of GCLc, GCLm, and SLC7A11 proteins. In vitro results showed that the IC_(50) of DDP in A549 was significantly declined under the conditioned medium treated with NWXF. Compared to the CAFs-CM+DDP group, the NWXF-CAFs-CM+DDP group displayed significantly increased apoptosis, significantly decreased levels of GSH and Cys, and significantly downregulated expressions of GCLc, GCLm, and SLC7A11 proteins. In conclusion, NWXF may ameliorate resistance to DDP in lung cancer by inhibiting CAFs-mediated GSH synthesis.

Guided by anti-tumor activity, components with anti-tumor effects were tracked and isolated from the leaves of Dendrobium nobile using silica gel column chromatography, gel column chromatography, medium-pressure preparative chromatography, and high-performance liquid chromatography. The structures of the purified monomer compounds were identified by comprehensive spectroscopic techniques including NMR and HR-ESI-MS. Five bibenzyl derivatives were isolated and identified from the leaves of D. nobile: crepidatuol C(1),(S)-4,5,9-trihydroxy-2-methoxy-9,10-dihydrophenanthrene(2), crepidatuol B(3), 4,5-dihydroxy-2-methoxy-9,10-dihydrophenanthrene(4), and 3',4,5'-trihydroxy-3-methoxybibenzyl(5). Among them, compounds 1 and 2 are new compounds, while compounds 3-5 were isolated from the leaves of D. nobile for the first time. The five identified bibenzyl derivatives were tested for in vitro anti-tumor activity, and results showed that compounds 1-5 exhibited selective inhibitory effects against four tumor cell lines, i.e., HeLa, MCF-7, A549, and MGC-803.

Gastrointestinal malignant tumors are a group of severely life-threatening tumors. Their incidence and mortality rates consistently rank among the top 10 cancers worldwide and are increasing year by year. Based on his long-term clinical practice, Professor Zhou Zhongying proposes the theory of "cancer toxin". The research team led by Professor CHENG Hai-bo further establishes the pathogenesis theory of cancer toxin, holding that cancer toxin is the key factor in the occurrence and development of tumors, and thus taking "anti-cancer and detoxification" as the basic therapeutic principle. With the vigorous promotion of TCM, various active ingredients of TCM are extracted and make a difference in tumor therapy. These active ingredients can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an active ingredient extracted from the skin of Bufo gargarizans with detoxifying, anti-swelling, and pain-relieving effects and is widely used in the treatment of intermediate and advanced tumors. Clinical studies have revealed that cinobufotalin enhances tumor control rates, prolongs survival time, improves quality of life, and reduces the incidence of adverse reactions when combined with chemotherapy, radiotherapy, or targeted therapies. The mechanism studies have demonstrated that cinobufotalin plays a therapeutic role by inhibiting cell proliferation and invasion, inducing tumor cell apoptosis, modulating immune response, reversing drug resistance, etc. This paper reviews the research progress on cinobufotalin from the perspective of pathogenesis theory of cancer toxin through summarizing domestic and international reported research on clinical application and mechanism of cinobufotalin against gastrointestinal malignant tumors in recent years. The findings aim to provide a theoretical basis for research on the anti-tumor effect of cinobufotalin and a reference for standardized use and in-depth research of drugs.

In recent years, immune checkpoint inhibitor (ICI) therapy has achieved a breakthrough in cancer treatment. By targeting and blocking immune checkpoint molecules on T cells, ICIs release inhibited anti-tumor immune responses, demonstrating durable clinical efficacy and improved long-term survival across multiple cancer types. However, only a minority of cancer patients currently benefit from ICI treatment, with primary resistance observed in most malignancies. Clarifying the mechanisms underlying primary resistance to ICI therapy is conducive to the development of effective combination strategies for overcoming drug resistance. This review systematically examines the molecular basis of primary resistance to ICIs through following aspects: tumor lymphocyte infiltration phenotype, interferon signaling pathways, antigen presentation machinery, and tumor cell-intrinsic oncogenic signaling pathways, which may provide novel therapeutic targets and rational combination strategies for cancer immunotherapy.

The ubiquitin-proteasome system (UPS) serves as the central mechanism for protein degradation in eukaryotic cells. Deubiquitinases (DUBs), which maintain protein stability and function by removing ubiquitin chains play a key role in protein cycling. Consequently, a DUB-targeting chimera (DUBTAC) technology has emerged. A DUBTAC consists of three components: a protein-targeting ligand, a DUB recruiter, and a linker connecting them. A DUBTAC can simultaneously bind to its targeted protein and DUB and induce the DUB to cleave the ubiquitin chains, thereby restoring the protein function by stabilizing the target protein. The DUBTAC technology provides a novel research strategy involving targeted protein stabilization for conventionally "undruggable" proteins that are abnormally degraded. Compared with other mature technologies, such as proteolysis-targeting chimera (PROTAC) and molecular glue degrader technologies, the DUBTAC technology has the unique advantages of targeting and stabilizing tumor suppressors, thus showing high potential for cancer therapy. However, it is still in the early stage of development with few systematic summaries of recent research achievements. This review introduces the basic concepts, critical design, and research considerations of DUBTACs, summarizes the latest research advances in DUBTAC technology for antitumor drug development, and discusses the development strategies and clinical application prospects of DUBTACs in the future, aiming to provide more directions for research on this technology.

Objective: The optimal adjuvant treatment regimen for pancreatic cancer after surgery remains undetermined. This study aimed to compare the efficacy and safety of S-1 combined with gemcitabine (GS) versus S-1 monotherapy in adjuvant therapy for pancreatic cancer. Methods: A retrospective analysis was conducted on postoperative pancreatic ductal adenocarcinoma (PDAC) patients who received GS or S-1 adjuvant chemotherapy at Peking Union Medical College Hospital from March 2016 to September 2024. Clinicalopathological characteristics, molecular features, treatment details, efficacy outcomes, and toxicity data were collected via electronic medical records and telephone follow-up. Results: A total of 454 patients were included, with 313 receiving GS and 141 receiving S-1. GS-treated patients were generally younger (median age: 62 vs. 66 years, P＜0.001). The median disease-free survival (DFS, 15.4 vs. 12.5 months, P=0.150) and overall survival (OS, 33.5 vs. 24.7 months, P=0.150) showed trends toward prolongation in the GS group compared with the S-1 group. In CA19-9-positive patients prior to adjuvant chemotherapy, GS therapy significantly prolonged DFS (10.7 vs. 8.8 months, P=0.040) and OS (28.2 vs. 19.8 months, P=0.003) compared with S-1 monotherapy. However, the GS group had a higher incidence of grade ≥3 adverse events [59.3%(128/216) vs. 39.4%(26/66), P=0.007], particularly neutropenia [40.7%(88/216) vs. 19.7%(13/66), P=0.003] and fatigue [19.0%(41/216) vs. 7.6%(5/66), P=0.045]. Molecular analysis revealed that TP53 gene variants may predict poor survival outcomes, but no association was observed between homologous recombination repair-related gene variants and treatment efficacy of GS or S-1. Conclusions: GS adjuvant therapy demonstrates trends toward improved DFS and OS compared with S-1 monotherapy in postoperative pancreatic cancer patients, though without statistical significance. GS was superior to S-1 in CA19-9-positive patients. The correlation between genetic mutation profiles and adjuvant treatment outcomes in pancreatic cancer requires further exploration.