Clinical & Translational Oncology最新文献

Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is a surrogate for long-term outcomes in breast cancer, yet response rates vary widely. Biomarkers are needed to predict efficacy. Vitamin D, through its receptor-mediated diverse biological effects on tumor biology and immune regulation, has been suggested as a potential predictor of pCR.

Methods: We retrospectively evaluated breast cancer patients who received NACT between December 2022 and December 2024. Baseline serum vitamin D and inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), and atherogenic index of plasma (AIP), were assessed. Pathological response was defined as pCR or Miller-Payne grades 4-5. ROC analysis identified optimal cut-offs, and logistic regression was applied to explore factors associated with pathological response.

Results: Among 223 patients, pCR occurred in 39.0%. ROC analysis identified 14.5 ng/mL as the optimal vitamin D threshold (AUC 0.705, p < 0.001). Vitamin D ≥ 14.5 ng/mL was independently associated with higher response, particularly in HR + /HER2 - and HER2 + subtypes; multivariable analyses also supported significance in TNBC. Recent vitamin D supplementation before NACT was significantly correlated with improved outcomes. Elevated CAR and AIP were inversely associated with response.

Conclusions: Vitamin D levels above 14.5 ng/mL independently predicted superior pathological response to NACT, with subtype-specific effects. Both baseline status and supplementation may enhance chemosensitivity, supporting vitamin D as a clinically relevant predictive biomarker.

Objective: To establish a patient-derived xenograft (PDX) model of testicular yolk sac tumor (TYST) that faithfully recapitulates the histopathological and molecular features of the primary tumor, thereby providing a robust pre-clinical platform for studying yolk sac tumor pathogenesis and evaluating novel therapeutics.

Methods: Patient-derived TYST tumor tissues were implanted subcutaneously in the right scapular region of immunodeficient mice (NPG and BALB/c nude strains) to generate a PDX model. Engrafted tumors were serially passaged and characterized by hematoxylin and eosin (H&E) staining, immunohistochemistry for AFP and SALL4, and PCR-based species identification to exclude murine lymphoma. The anti-tumor efficacy of the JEB regimen (carboplatin, etoposide, and bleomycin) was assessed using both in vivo experiments with the PDX model and ex vivo experiments utilizing the hydrogel-embedded histoculture drug sensitivity test (HDST).

Results: The patient-derived TYST tumor tissues exhibited higher tumorigenicity in NPG and BALB/c nude mice, maintaining stability through serial passaging. H&E staining confirmed preservation of characteristic yolk sac morphology, including Schiller-Duval bodies. Immunohistochemical analysis demonstrated consistent expression of AFP and SALL4 in PDX tumors, mirroring the diagnostic profile of the original specimen. PCR results confirmed the human origin of the xenografts and ruled out spontaneous murine lymphomas. HDST assays revealed marked sensitivity to the JEB regimen, which was corroborated in vivo: JEB treatment induced significant tumor regression without causing clinically relevant body weight loss.

Conclusion: We successfully established a TYST PDX model that retains tissue structure and protein expression signature of the patient's tumor tissue. Furthermore, this PDX model demonstrates high sensitivity to standard JEB chemotherapy and represents a valuable resource for translational research in pediatric germ cell tumors.

Background: Classic Kaposi's sarcoma (CKS) is an angiogenic tumor with no standardized treatment. Increased mTOR pathway activity in tumors fuels oncogenesis by stimulating anabolic metabolism, cell proliferation, and angiogenesis. This study aimed to assess the therapeutic potential of mTOR inhibitor metformin in CKS patients.

Methods: Two consecutive patients with biopsy-proven, CKS received metformin as monotherapy, and we further leverage single-cell RNA sequencing and spatial transcriptomics to uncover its underlying molecular mechanisms.

Results: Rapid clinical response with no adverse effects was observed in 2 CKS patients. Further investigation identified characteristic spindle cells (SCs) exhibiting heightened activity in VEGF, mTOR, and hypoxia signaling pathways, suggestive of a terminal stromal differentiation state. Besides, the immune landscape was characterized by a high proportion of CD8+ Tex and NK cells displaying suppressed cytotoxicity and migration functions. Crucially, SCs were found to interact with immune cells predominantly via the CXCL9-CXCR3 signaling axis.

Conclusion: This study reveals the mTOR-driven differentiation of SCs in KS pathogenesis aligning with rapid clinical improvement in CKS patients, which provides compelling evidence for metformin's therapeutic potential in CKS.

Purpose: Trastuzumab, the first anti-human epidermal growth factor receptor 2 (HER2)-targeted drug, is limited by adverse drug events (ADEs). The next-generation antibody-drug conjugates trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) exhibit enhanced efficacy and safety profiles compared with trastuzumab. In this study, we utilized US Food and Drug Administration Adverse Event Reporting System (FAERS) data to compare the ADEs of all three drugs, to facilitate personalized clinical decision-making and targeted monitoring.

Methods: ADE reports for patients with breast cancer using trastuzumab, T-DXd, or T-DM1 were retrieved. ADEs were classified using preferred terms (PT), standardized MedDRA queries (SMQs), and system organ classes (SOCs). Data mining using reported odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-Poisson shrinker was conducted.

Results: Overall, 20,829 cases of trastuzumab, 4565 cases of T-DXd, and 2975 cases of T-DM1 were included. With regard to SMQ terms, trastuzumab had a higher signal intensity for cardiac toxicity, and the RORs for "cardiomyopathy" of trastuzumab, T-DXd and T-DM1 were 8.59, 1.33, and 1.84, respectively. Meanwhile, T-DXd showed stronger signals for lung toxicity and T-DM1 showed prominent hepatotoxicity signals. Based on the differences between trastuzumab, T-DXd and T-DM1, this study established an individualized medication selection flowchart.

Conclusions: This study applied four algorithms to analyze and compare ADEs associated with trastuzumab, T-DXd, or T-DM1. By integrating multi-level analysis including PT, SMQ, and SOC, this study provides a comprehensive safety perspective to guide clinical decision-making and medication monitoring for patients with breast cancer receiving HER2-targeted therapy.

Introduction: Social determinants of health (SDOH) significantly influence cancer development, treatment response, and clinical outcomes. However, their integration into oncology clinical practice remains limited. In this study, the perceptions of oncology health care professionals regarding the influence of SDOH and the existing barriers to addressing them within the Spanish health care system.

Materials and methods: This cross-sectional study was conducted using a self-administered questionnaire distributed to oncology professionals in various autonomous communities in Spain. Sociodemographic variables, professional roles, perceptions of the impact of SDOH, and perceived barriers to addressing these social factors were analyzed. Descriptive and inferential statistics (chi-square test and Fisher's exact test) were applied.

Results: A total of 258 professionals, mainly from medical oncology, nursing, and oncology pharmacies, participated in the study. More than 80% considered that SDOH influences cancer development and prognoses, and nearly 70% considered that SDOH influences treatment toxicity. Significant differences in knowledge levels were identified by professional role, with the most significant lack of knowledge noted in nursing, pharmacy, and radiophysics. The main barriers reported were time constraints, resources, specific protocols, and training in social and cultural competencies.

Conclusions: There is a high level of awareness regarding the relevance of SDOH in oncology, although knowledge gaps and structural obstacles persist. Therefore, it is imperative to develop training and institutional interventions that integrate the social component into oncology care, thereby promoting more equitable and patient-centered clinical practice.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality. Although Synaptotagmin 8 (SYT8) has been implicated in tumorigenesis, its role in CRC is poorly understood.

Methods: Transcriptomic and clinical data from TCGA and five GEO datasets were analyzed, and survival analysis together with nomogram modeling was applied to evaluate the prognostic value of SYT8. Functional enrichment and immune infiltration analyses were performed to investigate its potential roles and its impact on the tumor microenvironment. SYT8 expression in CRC and adjacent normal tissues was validated by qRT-PCR and western blotting. Knocking down experiments in vitro were conducted to assess its effects on cell proliferation, migration, and related signaling pathways.

Results: Compared to normal samples, SYT8 was significantly highly expressed in CRC tissues. Additionally, elevated SYT8 expression was strongly associated with poorer overall survival and identified as an independent prognostic factor. Functional enrichment analysis indicated its potential involvement in multiple signaling pathways, including MAPK and PI3K-Akt. Immune-related analyses revealed that tumors with high SYT8 expression exhibited increased Treg infiltration and upregulation of immune checkpoint molecules PDCD1 and LAG3. Significantly, downregulation of SYT8 suppressed HT29 cell viability, proliferation, and migration. Moreover, SYT8 downregulation notably reduced the phosphorylation of Akt and ERK1/2 in HT29 cells.

Conclusions: SYT8 plays a critical role in the development and progression of CRC and holds potential as a prognostic biomarker, as well as a novel therapeutic target.

Purpose: Adherence to adjuvant endocrine therapy (AET) is critical for breast cancer prognosis, yet there is a current lack of convenient predictive tools that integrate multidimensional factors. This study aimed to develop a nomogram prediction model for forecasting AET adherence in breast cancer patients.

Methods: Clinical data from 403 breast cancer patients were collected and analyzed. Patients were randomly divided into training (n = 281) and validation (n = 122) cohorts at a 7:3 ratio. Risk factors influencing treatment adherence were screened using univariate and multivariate logistic regression. The nomogram was constructed and validated using R software, with its predictive performance and clinical utility evaluated through receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).

Results: Multivariate analysis identified medical insurance type (OR = 3.435, 95% CI: 1.230-9.592, P = 0.019), psychological assessment (OR = 0.779, 95% CI: 0.712-0.853, P < 0.001), and perceived social support (OR = 1.131, 95% CI: 1.088-1.177, P < 0.001) as independent predictors of AET adherence. The resulting nomogram achieved AUC values for the training cohort and validation cohort of 0.933 (95% CI: 0.905-0.961) and 0.891 (95% CI: 0.826-0.957), respectively. Calibration curves and DCA demonstrated excellent consistency and clinical applicability.

Conclusions: The study identified medical insurance type, psychological assessment, and perceived social support as key factors influencing adherence to AET. The developed nomogram on this basis provides a visual tool for identifying high-risk populations with poor adherence to AET, which helps to carry out personalized interventions for different patients in the future.

Colorectal cancer (CRC) is caused by a complex interaction between genetic, environmental, and microbial risk factors, and intestinal microbiota has critical roles in inflammation, immunology, and epithelial integrity. Pathobionts from the intestines (Fusobacterium nucleatum, Bacteroides fragilis, and E. coli that produce colibactin) promote DNA damage, immunity protection from cancer therapy, and resistance to chemotherapy treatments. The beneficial commensals and metabolites of intestinal microbes (namely butyrate) increase the mucosal immune response and inhibit tumor-specific signaling mechanisms. Microbe controlled changes of populations of myeloid, lymphoid, and regulatory cells dictate the state of the tumor-immune system and provide actionable checkpoints and biomarkers for cancer therapy. An enormous variety of clinical interventions based on the gut microbiota (probiotics, prebiotics, and fecal microbiota transfer) and diagnostic approaches is currently being developed. Translational issues are difficult due to the interindividual variability and regulatory complexity of tumors. Research needs include standardizing multi-omics data from multidisciplinary teams and mechanistic validation in organoid and gnotobiotic models as well as prediction algorithms to optimize the microbiome-based medicine for individual patients. Targeting the immune-microbiota axis may provide new therapeutic strategies in the diagnosis, prognosis, and therapy of CRC.

Purpose: The early diagnosis of malignant transformation in oral leukoplakia (OLK) assumes paramount importance in the preventive and timely intervention strategies for oral cancer. Nevertheless, the existing diagnostic modalities exhibit complexity, invasiveness, or inherent limitations. The therapeutic efficacy and mechanism of miR-185 in extracellular vesicles (EVs) in oral cancer have been previously demonstrated. Thus, this study aims to establish a diagnostic model using miR-185 from salivary EVs to identify the malignant transformation of OLK and facilitate the prevention and treatment of oral cancer.

Methods: miR-185 in salivary EVs was characterized in a discovery cohort comprising healthy controls (n = 8) and patients with hyperplasia (n = 13), mild to moderate dysplasia (n = 15), severe dysplasia (n = 10), and squamous cell carcinoma (OSCC, n = 23). A training set from a validation cohort (n = 164) underwent analysis using receiver operating characteristic curve (ROC) and logistic regression analysis to distinguish malignant forms (MT; i.e., severe dysplasia and OSCC) from non-malignant forms (N-MT; i.e., hyperplasia, mild to moderate dysplasia). The validation set was then utilized to validate the model.

Results: miR-185 in salivary EVs demonstrated accurate identification of MT [area under ROC (AUC) = 0.9349, specificity = 90.32%, sensitivity = 80.77%], and its feasibility and accuracy were successfully confirmed in the validation set (specificity = 93.55%, sensitivity = 84.21%).

Conclusion: miR-185 in salivary EVs can serve as a non-invasive biomarker for the detection of OLK malignant transformation.

Esophageal neuroendocrine carcinoma (ENEC) is a rare and aggressive malignancy, characterized by its high-grade, poorly differentiated nature. Despite advancements in understanding neuroendocrine tumors (NETs), ENEC remains an under-researched and poorly understood entity, presenting significant challenges in both diagnosis and treatment. Molecular studies have revealed frequent mutations in TP53 and RB1, along with genetic profiles paralleling small cell lung cancer (SCLC), suggesting shared oncogenic pathways that may guide targeted therapeutic approaches. However, the rarity of ENEC has limited the development of standardized treatment regimens, with most strategies borrowed from other malignancies such as SCLC. Current treatments, including platinum-based chemotherapy, show moderate success, yet response rates remain variable, particularly in advanced stages. The role of immunotherapy and targeted therapies is under investigation, with promising case reports but limited clinical evidence. Emerging diagnostic technologies, such as molecular profiling and liquid biopsy, offer enhanced precision in early detection and personalized treatment plans. Prognostic factors, such as Ki-67 proliferation index, serum biomarkers, and tumor stage, have shown significant associations with survival outcomes, though they remain under-explored in prospective clinical trials. Given the unique molecular features of ENEC, including high tumor mutational burden and distinct immune profiles, further research is essential to develop effective biomarkers, refine prognostic models, and create personalized, targeted therapies. This review aims to consolidate current knowledge on ENEC's molecular biology, diagnosis, and treatment, while identifying gaps in research and suggesting directions for future investigation to improve patient outcomes.