Whether to change adjuvant regimen after ineffective neoadjuvant chemotherapy in locally advanced gastric cancer (LAGC) remains unclear. We conducted an exploratory study on whether graded histologic regression (GHR) < 50

Excessive proliferation of crypt stem cells represents a crucial hallmark in colorectal tumorigenesis. G protein-coupled receptor 182 (GPR182), a recently partially "deorphanized" G protein-coupled receptor (GPCR), has emerged as a pivotal modulator in gastrointestinal tumors. However, its roles and underlying mechanism in colorectal tumors remain unclear, primarily due to the absence of identified endogenous ligands. In this study, we identified Insulin like growth factor binding protein 5 (IGFBP5) as a novel endogenous ligand for GPR182. GPR182 mRNA and protein expression levels were significantly up-regulated in cancer stem cells of colorectal tissues or cell lines. Functional assays revealed that IGFBP5 inhibited growth of intestinal crypt organoids and cancer stem cell spheres. In APCMin/+ mice, IGFBP5 administration attenuated the tumor development while co-administration of GPR182 knockdown adeno-associated virus (AAV) abrogated this phenotype. Consistently, systemic IGFBP5 knockout markedly accelerated tumorigenesis and shortened survival time in APCMin/+ mice. Mechanistic investigations demonstrated that IGFBP5's engagement with GPR182 induced inhibition of AKT/P70S6K pathway via Protein kinase C alpha (PKCα) dephosphorylation. Together, these findings elucidate the suppressive role of IGFBP5 in colorectal cancer (CRC) stem cells via GPR182/PKCα/AKT/P70S6K axis, highlighting IGFBP5 implementation a promising strategy for CRC.

Background:Mitochondrial-related pathways (MRPs) play a crucial role in cancer metabolism and progression; however, their prognostic value in breast cancer (BC) is still poorly understood. Methods:We integrated multiomics data to investigate the landscape of MRPs in BC. A mitochondria pathways-associated signature (MPAS) was established using multimachine learning framework and interpreted by SHAP analysis across independent BC cohorts. Additionally, a series of functional experiments were employed to explore the role of RNA exonuclease 2 (REXO2) in BC cells. Results:MRPs are extensively activated in BC at multiomics level. MPAS demonstrates outstanding predictive performance across multiple BC cohorts, with high scores indicating poor clinical outcomes. Moreover, it was observed that high MPAS scores are closely associated with immunosuppressive states and inflammatory microenvironments. SHAP analysis identified REXO2 as a hub factor of MPAS. Cell-based work confirmed that silencing REXO2 greatly inhibited cell proliferation and induced apoptosis in BC. Conclusions:Our proposed MPAS could effectively evaluate the prognosis and treatment response of BC patients, providing new reference for clinical decision-making. Furthermore, REXO2 regulates cell proliferation and apoptosis, making it a promising potential therapeutic target for inhibiting BC progression.

Occult breast cancer (OBC) is a rare subtype characterized by axillary lymph node (LN) metastasis without an identifiable primary breast lesion. Owing to its rarity, optimal management remains controversial. We performed a systematic review and meta-analysis to comprehensively evaluate the clinicopathological characteristics, prognosis, and treatment outcomes of female patients with OBC. A systematic review and meta-analysis were conducted using PubMed/MEDLINE, Embase, and the Cochrane Library to identify eligible studies published after 2000. Female patients with OBC (T0N+M0) were included. Primary outcomes were overall survival (OS) and disease-free survival (DFS), analyzed according to LN stage and treatment strategies. Thirty retrospective studies involving 6,001 patients were included. The pooled treatment proportions were 30

Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as a paradigm-shifting therapeutic strategy in oncology, demonstrating significant synthetic lethality in tumors characterized by homologous recombination deficiency. Due to their substantial efficacy, PARP inhibitors (PARPi) have received approval for the treatment of four malignancies: ovarian cancer, breast cancer, prostate cancer, and pancreatic cancer. However, the specific clinical indications and optimal utilization settings vary among these types of cancers. Identifying novel biomarkers is thus essential for accurately predicting patients’ responses to PARPi, therefore enhancing effective patient stratification. Notably, the emergence of acquired resistance to PARPi presents a considerable challenge to their practical implementation in clinical practice. Both preclinical and clinical studies have elucidated numerous molecular alterations contributing to this resistance, offering valuable insights into potential strategies for overcoming it. This review comprehensively summarizes landmark clinical trials involving both PARPi monotherapy and various combination strategies, and outlines future research directions. We compare existing predictive tools for resistance to PARPi, aiming to refine future clinical applications and identify critical gaps requiring further investigation. This review also presents new insights into primary and acquired resistance by updating mechanisms of PARPi action and summarizing the biological processes involved in PARPi resistance. Additionally, we discuss potential strategies designed to overcome these mechanisms.

Gastric cancer (GC) remains a leading cause of cancer-related morbidity and mortality worldwide, with poor prognosis for advanced-stage patients. Therefore, in-depth exploration of the mechanisms underlying GC initiation and progression, as well as the development of novel therapeutic strategies, is of crucial importance. Cellular senescence is a stable cell cycle arrest program that plays a dual role in GC. It exerts tumor-suppressive effects via growth arrest but also promotes tumor progression and immune evasion by remodeling the tumor microenvironment (TME) through senescence-associated secretory phenotype (SASP). This review comprehensively elucidates the molecular mechanisms of cellular senescence in GC and the core regulatory networks involving gene regulation, epigenetic modifications, metabolic reprogramming, and cell cycle arrest. Additionally, the review highlights how senescent cells foster an immunosuppressive microenvironment via SASP, forming a self-reinforcing feed-forward loop. Regarding therapeutic strategies, we summarize potential approaches targeting cellular senescence, including senescence induction, senescent cell clearance, SASP modulation, and multi-target synergistic therapy by integrating epigenetic regulation, metabolic intervention, and immune microenvironment modulation. Despite progress, numerous challenges remain. Future studies should leverage multi-omics technologies, novel models' development, and large-scale clinical trials to advance the clinical translation of GC cellular senescence research, providing new insights for improving prognosis.

BackgroundTrials show that sentinel lymph node biopsy (SLNB) can replace completion axillary lymph node dissection (ALND) for selected cN0 patients without compromising survival but real-world evidence from non-Western settings especially on regional nodal control remains limited.MethodsWe identified 53,758 female patients with cN0, pT1-3, pN0–1 breast cancer from the National Cancer Center Oncology Information Database (2013-2022). For pN1, survival analyses were restricted to 2017-2022. Propensity score matching and competing-risks models were employed to compare overall survival, breast cancer specific survival, and regional nodal recurrence (RNR) between SLNB and ALND.ResultsSLNB use increased from 18.8% to 75.3% in pN0 and from 9.7% to 48.2% in pN1. In pN0, 5-year RNR was similar for SLNB versus ALND (1.06% vs 0.96%; adjusted SHR 1.03). In pN1, SLNB was associated with higher 5-year RNR after breast-conserving surgery (BCS) (4.99% vs 1.27%; adjusted SHR 4.44; P = 0.033), most pronounced for Ki-67 ≥30% (SHR 12.79; P = 0.012) and no special type histology (SHR 5.90; P = 0.017). In the mastectomy cohort, 5-year RNR did not differ between SLNB and ALND (3.01% vs 2.05%; P = 0.946; adjusted SHR 1.22), except among patients without endocrine therapy (SHR 6.28; P = 0.01).ConclusionAxillary de-escalation has been widely adopted in China and appears oncologically safe for patients with pN0 disease and for those with pN1 disease undergoing mastectomy. In contrast, among patients with pN1 disease treated with breast-conserving surgery, SLNB was associated with a higher risk of regional nodal recurrence. When ALND is omitted, guideline-concordant adjuvant management may be important to maintain regional control.

Photo-initiated bioorthogonal reactions in the visible-light range allow spatiotemporal labeling or regulation in living systems, which however still remain scarce. To bridge this gap, we established a bioorthogonal o-dione and vinyl ether photocycloaddition (DVPC) reaction driven by visible light as the first-generation o-dione based bioorthogonal reaction (DVPC 1.0). Driven by the demand to expand substrate scope to include electron-rich alkenes with better stability, increased reaction rates and longer excitation wavelengths, herein we report the second-generation DVPC (DVPC 2.0) between o-diones and vinyl amides. Electron-withdrawing substitutions on the o-dione substrates in DVPC 2.0 were found to accelerate the reaction in aqueous solution by up to 50-fold. Some of the DVPC 2.0 substrates allowed two-photon excitation, which red-shifted the excitation wavelength to 700-800 nm. A bifunctional bioorthogonal substrate containing both an N-vinyl group and an azide functionality was prepared, which allowed sequential bioorthogonal reactions on proteins with temporal control.

Backgroud:Ureteritis and cystitis is a rare immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs), challenging to distinguish from urinary tract infection (UTI), easily leading to missed diagnosis. We aim to describe clinical features, radiological characteristics and treatment of patients who suffer from ICI-related ureteritis and cystitis (ICI-UC). Methods:This was a single centre case series of patients diagnosed with solid tumor who received ICIs treatment and subsequently suffered from ICI-UC. All clinical demographic data, laboratory parameters, imaging characteristics, and treatment information were collected. Results:Between Mar 1st, 2020 and Mar 31th 2025, 12 of 1239 patients treated at Peking Union Medical College Hospital with ICIs were confirmed to have ICI-related ureteritis and cystitis (0.96%), 10 males and 2 females. Only 1 patient received anti-programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4) dual immunotherapy, the other 11 patients received PD-1/PD-ligand 1 plus chemotherapy or/and target therapy. The median time to onset was 83 days (range 28-442 days). All patients (100%) exhibited significant urinary tract irritation symptoms. 12 patients demonstrated characteristic imaging abnormalities, including hydroureteronephrosis, irregular ureteral wall thickening, bladder wall thickening with irregular margins, or/and conspicuous renal fascia. Spontaneous remission was observed in 2 patients, while 10 patients received steroids and all showed rapid improvement of symptom after treatment.The median time from symptom onset to the initiation of steroids was 24 days, and the median prednisone dose was 0.60 mg/kg/day. Six patients (6/10, 60%) experienced disease recurrence during the corticosteroid tapering phase, and two patients who failed steroid tapering were successfully treated with a combination of corticosteroid and JAK inhibitor therapy. Conclusion:This pioneering cohort study provides the first systematic investigation of ICI-UC, establishing its incidence and comprehensively characterizing clinical and imaging features. Through cohort analysis, we propose a novel severity grading system with corresponding treatment algorithms, while additionally exploring the therapeutic potential of JAK inhibitors for steroid-dependent cases.

[This corrects the article DOI: 10.3389/fonc.2026.1809288.].

BACKGROUND:De novo metastatic breast cancer-defined by distant metastases at diagnosis-poses treatment challenges. While systemic therapy is standard, the benefit of primary tumor surgery remains debated. This study compared surgical patterns and survival in China versus the USA to provide evidence for personalized strategies. PATIENTS AND METHODS:In this multicenter retrospective cohort study, patients with surgically treated de novo metastatic breast cancer were identified from the National Cancer Center Oncology Information Database (NCCOID; n = 2037, 2013-2020) and Surveillance, Epidemiology, and End Results (SEER) (n = 3175, 2013-2020). Clinical features, treatments, and overall survival (OS) were contrasted. Kaplan-Meier curves and multivariable Cox models identified OS predictors. RESULTS:Compared with SEER, NCCOID patients were younger and had more T2 tumors; mastectomy predominated in both, though breast-conserving surgery was more frequent in SEER, and preoperative systemic therapy was more common in NCCOID. NCCOID achieved superior OS (1 year, 3 year, 5 year: 91.5%, 77.4%, 67.9%, respectively) versus SEER (87.7%, 62.8%, 46.4%). Improved survival was seen in hormone-receptor-positive tumors, smaller primary lesions (lower T category), and bone-only metastases. Multivariate analysis confirmed age 35-54 years, HR+ and HER2+ status, and limited (especially bone-only) metastases as independent favorable factors. CONCLUSIONS:Surgical management of de novo metastatic breast cancer differs between China and the USA. Select patients-particularly those with HR+ or HER2+ tumors, small primaries, and limited metastases-may benefit from resection, underscoring the need for multidisciplinary, personalized decision-making and prospective validation of optimal surgical timing.

Rationale: Multiple primary malignant neoplasms (MPMNs) is a rare condition in tumor diagnosis. Recently, medical workers have commenced to pay attention to this. Clinical features and diagnoses: A 72-year-old female was admitted to our hospital for touching a painless lump in her right-upper breast. She also complained of incidental finding of another painless lump in her left groin shortly after her finding in breast tumor. Ultrasound showed a 1.2* 0.5 cm hypo-echoic nodule in the right-upper breast with an irregular form and unclear margin. For the left inguinal lump, it was scanned by ultrasound as an inguinal lymph node with a size of 2.8 * 1.2cm, with cortical thickening and eccentric lymphatic hilum. An enhanced magnetic resonance imaging showed bilateral multiple enlarged lymph nodes with uniformed enhancement. Interventions and outcomes: An ultrasound-based fine-needle biopsy of the breast tumor was firstly conducted and the pathological result did not show any malignancy. Then an excision biopsy of the tumor was conducted and the intraoperative frozen section indicated “breast invasive cancer”. Subsequently, a breast-conserving surgery with sentinel lymph node biopsy in the right armpit was performed. The intraoperative frozen biopsy suggested a negative results in the margin tissues but cancerous tissue was detected in one of six sentinel lymph nodes(1/6). Then the axillary lymph node dissection was performed and the final paraffin section results indicated “non-specific invasive breast cancer, tumor size: 1.3* 0.6* 0.5cm, Grade II; axillary lymph node metastasis (1/27); stage: pT1cN1a”. After the breast operation, she went to outpatient clinics of bone tumor and received an ultrasound fine-needle biopsy of the enlarged left inguinal lymph node where she referred to previously. Both the result of immunohistochemistry and gene rearrangement test supported a diagnosis of follicular lymphoma (FL, Grade 2). Besides subsequent adjuvant chemotherapy and radiotherapy for her primary breast cancer, the patient regularly followed up her condition of FL. Lessons: MPMNs always tend to be misdiagnosed as a locoregional or distal metastatic tumor, especially for lymph node found in different parts of the body. It is easy to cause a delayed or erroneous treatment. An in-time and comprehensive clinical examination, medical imaging, and proper approach of pathological biopsy are essential for an effective management of MPMNs. Citation Format: Zijun Zhao, Qingyao Shang, Chenxuan Yang, Jiaxiang Liu, Jiabin Wang, Xiyu Kang, Jiaxian Yue, Xin Wang, Xiang Wang. Synchronous female breast cancer and follicular lymphoma in a single patient: A case report [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-08-21.

Background: The survival outcomes of carboplatin plus taxane neoadjuvant chemotherapy(NAC) in triple negative breast cancer(TNBC) was lack of a large-sample study. The predictive biomarker of efficacy based on cell-free DNA (cfDNA) whole-methylome sequencing (WMS) has not been reported yet. Methods: The prospective multi-center cohort study was conducted in four hospitals of China between 2016 and 2023. Stage II-III TNBC patients were enrolled to receive NAC of carboplatin (AUC 5) every 3 weeks or carboplatin (AUC 4) every 2 weeks plus taxane(standard dose) for 4-6 cycles. Plasma samples were prospectively collected at baseline(T1) and end of NAC (T2). Chromosomal aneuploidy of featured fragments (CAFF), fragment size index (FSI) and methylation density score (MD) of cfDNA were detected with WMS. The primary endpoint were relapse-free survival (RFS) and exploratory biomarker analysis. Result: A total of 267 patients were included in the study. The median age was 49 years, 156 patients (58.4%) were stage III disease. cT3-T4 were 28.1% (75/267), cN3 were 17.2% (46/267). 40.3% patients (106/263) achieved pathologic complete response (pCR). The 3-year RFS and overall survival (OS) were 77.9%, 87.6%, respectively. Patients who achieved pCR had a significant better RFS(95.5%) and OS(97.7%) than those non-pCR (68.5%, 81.2%, all P<0.001). Survival of patients with minimal residual disease (ypT1mi/1a/1b N0) are comparable to those pCR, 3-year RFS and OS were 80.2% vs 92.3%(Log-rank P=0.060), 90.5% vs 97.4% (Log-rank P=0.247), respectively, after excluding cN3 patients. Patients with residual node number >2 had a poor 3-year RFS and OS compared to number≤2( All Log-rank P<0.0001). A total of 66 patients with 120 plasma samples (64 samples at T1, 56 samples at T2) were included in WMS analysis. Patients with CAFF, FSI or MD positive at T1 had a higher tumor burden (stage III or cN2-3, all P values <0.05). The proportion of patients with FSI negative at T2 was significantly higher in pCR group compared to non-pCR(86.2% vs 59.3%,P=0.034). Similar tendency were observed in patients with CAFF negative. A linear SVM model was developed to predict pCR with an AUC of 0.90 in the training datase and an AUC of 0.86 in the testing dataset. Moreover, patients with MD positive at T1 was significantly associated with poor RFS compared to MD negative (HR = 7.36, Log-rank P=0.028). Conclusion: Our large-sample study further confirmed that carboplatin plus taxanes as NAC in TNBC was a preferred regimen with the comparable survival outcome, especially for patients who cannot tolerate anthracyclines or immunotherapy. Biomarkers based on cfDNA WMS may provide predictive and prognostic information, warranting further investigation. Citation Format: Xi Chen, Meng Xiu, Hua Kang, Yan Zhang, Hua Yang, Qiao Li, Qing Li, Xueyan Cheng, Jiayu Wang, Ying Fan, Bo Lan, Bin Hua, Min Xiao, Xiaoyan Qian, Xiang Wang, Binghe Xu, Pin Zhang. Survival outcomes of carboplatin plus taxanes neoadjuvant chemotherapy in triple negative breast cancer and cell-free DNA whole methylome based biomarker analysis: A prospective multi-center cohort study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-09-19.

OBJECTIVES:Gastric cancer (GC) remains a significant public health challenge, with accumulating evidence indicating an association between socioeconomic status (SES) and GC risk. This study aimed to examine the independent and synergistic effects of SES and lifestyle on GC incidence within a large prospective cohort. STUDY DESIGN:Prospective cohort study. METHODS:Data were analysed from 349,908 UK Biobank participants using latent class analysis to determine SES (household income, education, employment). Lifestyle was assessed based on smoking status, alcohol consumption, physical activity, body mass index and diet. Multivariable Cox regression tested associations between SES, lifestyle and GC, with mediation and interaction analyses used to explore their relationships. RESULTS:SES was significantly associated with GC risk (hazard ratio [HR] = 1.35, 95 % confidence interval [CI], 1.20-1.52). An unhealthy lifestyle was also linked to increased GC risk (HR = 1.48, 95 % CI, 1.30-1.68). Individuals with low SES and an unhealthy lifestyle had a 195 % higher risk of GC compared to those with high SES and a healthy lifestyle (HR = 2.95, 95 % CI, 2.11-4.11). Mediation analysis indicated that 5.26 % of the SES-GC risk association was mediated by lifestyle factors. No significant interaction between SES and lifestyle was observed. CONCLUSIONS:Low SES was related to an increased risk of GC, some of which may be mediated by unhealthy lifestyle. Public health initiatives should focus on addressing socioeconomic disparities and improving lifestyle factors to reduce GC incidence.

Background Breast cancer remains one of the most common malignancies globally. With advancements in systemic therapies and radiation, breast-conserving surgery (BCS) has emerged as a preferred option for early-stage breast cancer. However, real-world studies comparing BCS and mastectomy outcomes, especially in China, are limited, necessitating further exploration of patient selection, survival outcomes, and economic implications. Method A retrospective cohort study was conducted using the National Cancer Center Oncology Information Database (NCCOID) in China, covering 2013 to 2022. Female patients diagnosed with early-stage breast cancer who underwent either BCS or mastectomy were included. Clinical outcomes, causes of death, and medical expenses were analyzed. The primary endpoint was overall survival (OS), and the secondary endpoint was breast cancer-specific survival (BCSS). Statistical analyses included Kaplan-Meier survival curves and Cox regression models. Results This study included 114,094 female breast cancer patients, with 20.6% undergoing BCS and 79.4% for mastectomy. BCS showed higher 5-year OS (97.9% [95% CI 97.7%-98.2%] vs . 95.3% [95% CI 95.1%-95.5%], p < 0.001) and BCSS (99.0% [95% CI 98.9%-99.2%] vs. 97.4% [95% CI 97.2%-97.5%], p < 0.001) than mastectomy. The BCS group was associated with lower mortality from both breast cancer and cardiovascular diseases compared to the mastectomy group, with statistically significant differences observed ( p < 0.001). The BCS group incurred higher costs than the mastectomy group across all stages (78,610.63 RMB vs. 68,995.82 RMB, p < 0.001). Conclusion The BCS rate has increased from 2013 to 2022. Patients undergoing BCS have better OS and BCSS than mastectomy despite higher expenses resulting from BCS.

Objective:This study was aimed at investigating if the lymph node aspirated wash-out liquid thyroglobulin level and thyroid imaging reporting and data system (TI-RADS) nodule score can be the predictive factor for cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC). Methods:The study included 251 patients with surgically confirmed PTC. All the patients underwent preoperative thyroid and cervical ultrasound examination using ACR TI-RADS classification, fine-needle aspiration biopsy (FNAB) for BRAF V600E gene detection, and thyroglobulin (Tg) detection in lymph node aspiration fluid. The results of these examinations and tests were statistically analyzed. A binary logistic regression model was used to determine the predictive impact of Tg levels, gene mutation status, and TI-RADS nodule score on lymph node metastasis. Results:Among the enrolled patients, 219/251 (87.25%), had BRAF V600E gene mutations and 132/251 (52.59%) had cervical lymph node metastasis. The Tg level in the lymph node aspiration fluid of patients with metastasis was significantly higher than in those without metastasis (324.94 ± 192.52 ng/mL vs 67.93 ± 136.62 ng/mL, P = 0.000), but there was no significant difference in serum Tg levels between the two groups (27.08 ± 71.60 ng/mL vs 20.73 ± 55.21 ng/mL, P = 0.276). The area under the ROC curve (AUC) for lymph node aspiration fluid Tg was 0.858. Thyroglobulin level has a significant positive effect on lymph node metastasis, with a regression coefficient of 0.003 and P = 0.000 < 0.001. BARF V600E mutation status and TI-RADS nodule score do not have a significant effect on lymph node metastasis, with P-values greater than 0.05. Conclusion:Thyroglobulin levels of lymph node aspiration fluid has a good predictive value for the diagnosis of cervical lymph node metastasis in PTC patients with larger nodules.