Background: Gamma-glutamyl transferase 6 (GGT6) belongs to the GGT family and its functional mechanisms in colorectal cancer (CRC) are still not well understood in the academic community. This study aims to fill this research gap by examining the clinical relevance and biological effects of GGT6. Methods: GGT6 expression and clinical data were integrated from The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), and Gene Expression Omnibus (GEO) databases. Prognostic value was assessed using Kaplan-Meier (K-M) and Cox regression. Biological pathways and immune landscapes were analyzed via Gene Set Enrichment Analysis (GSEA), CIBERSORT, and Tumor Immune Dysfunction and Exclusion (TIDE). Findings were validated using tissue microarrays and in vitro assays, including Cell Counting Kit-8 (CCK-8), colony formation, and transwell assays in HT-29 and DLD-1 cell lines. Results: GGT6 was significantly downregulated in CRC tissues, and its low expression served as an independent prognostic factor for poor survival. Functional analysis linked GGT6 to peroxisome proliferator-activated receptor (PPAR), epithelial-mesenchymal transition (EMT), and KRAS signaling. Importantly, knockdown of GGT6 significantly promoted the proliferation, migration, and invasion of HT29 and DLD-1 cells. Furthermore, GGT6 expression correlated with immune infiltration and predicted sensitivity to common therapeutic drugs. Conclusions: GGT6 acts as a tumor suppressor in CRC. Its downregulation promotes malignant progression and correlates with poor prognosis, making it a promising biomarker and potential therapeutic target.

Metabolic perturbations in the tumor microenvironment profoundly compromise the stemlike properties and effector functions of CD8 T cells. Deciphering the metabolic circuitry that sustains T cell stemness is critical for reinvigorating tumor-infiltrating lymphocytes and augmenting immunotherapeutic efficacy. Here, we identify citraconate, an itaconate isomer, as a metabolite markedly depleted in CD8 T cells subjected to chronic antigen stimulation or hypoxic conditions. Citraconate supplementation preserves stemlike characteristics, attenuates ferroptosis, and potentiates T cell-mediated antitumor immunity. Mechanistically, citraconate maintains intracellular cyclic adenosine monophosphate (cAMP) concentrations by suppressing phosphodiesterase1A/C (PDE1A/C) expression and preserving mitochondrial integrity, thereby activating protein kinase A (PKA) signaling. This activation transcriptionally represses arachidonate-5-lipoxygenase (ALOX5), consequently reducing arachidonic acid peroxidation. Clinically, diminished ALOX5 or PDE1A expression correlates with reduced T cell exhaustion and improved responses to immune checkpoint blockade (ICB) therapy. Our findings reveal the citraconate-mediated PDE1-cAMP-ALOX5 axis as a potential therapeutic target for enhancing cancer immunotherapy.

Colorectal cancer (CRC) and colorectal liver metastasis (CRLM) posed significant challenges in cancer management. To develop more effective therapies, we investigated the role of Farnesoid X Receptor (FXR, Nr1h4) in the tumor-liver microenvironment, an area with substantial therapeutic potential that had been underexplored. Employing preclinical mouse models of CRLM, we conducted a comprehensive evaluation of FXR expression and its functional significance in modulating the tumor-liver microenvironment. Techniques utilized included histological analysis, single-cell sequencing, immunohistochemistry (IHC), flow cytometry (FCM), and enzyme-linked immunosorbent assay (ELISA). Antibody depletion experiments, as well as the use of inhibitors and antagonists, were conducted to elucidate the mechanisms underlying FXR's role in colorectal cancer liver metastases. Our findings indicated that FXR knockout or treatment with Ursodeoxycholic Acid (UDCA) promoted CRLM. Single-cell sequencing, FCM, and antibody depletion experiments revealed that FXR affected CRLM prognosis by altering the liver microenvironment, with myeloid-derived suppressor cells (MDSCs) identified as the primary cellular mediators in this process. Mechanistically, the gutFXR-FGF15-PPARγ-VEGFα-MDSC axis played a crucial role in MDSC accumulation, thereby promoting liver metastasis of colon cancer. Our study uncovered a novel function of FXR in regulating the liver microenvironment and influencing CRLM progression. Targeting the gutFXR-FGF15-PPARγ-VEGFα-MDSC axis may offer a promising therapeutic strategy for the prevention and treatment of CRLM.

e14598 Background: Immune checkpoint inhibitors (ICIs) have shown remarkable efficacy in microsatellite instability-high (MSI-H) colorectal cancer (CRC). However, a substantial subset of patients fails to achieve durable clinical benefit. BRAF mutations—particularly BRAF V600E —are associated with aggressive tumor behavior and poor clinical outcomes, and targeted therapies provide effective treatment options. Epidemiological studies reveal that BRAF mutations frequently coexist with MSI-H status. Nevertheless, the optimal treatment strategy for MSI-H BRAF V600E CRC remains unclear, including whether these patients benefit most from ICIs alone, targeted therapy alone, or combined ICIs and targeted therapy therapy. This study aims to comprehensively characterize the biological properties and tumor immune microenvironment (TME) in MSI-H BRAF V600E CRC, with the goal of improving therapeutic strategies for MSI-H BRAF V600E CRC. Methods: MSI-H BRAF WT and MSI-H BRAF V600E cell lines were generated from the MC38 background. The biological behaviors of cells were evaluated using colony formation, CCK-8, transwell, and Western bloting. Flow cytometry and multiplex immunofluorescence were performed to evaluate immune cell infiltration. RNA sequencing was conducted to explore underlying molecular mechanisms. Therapeutic efficacy was assessed in vivo across four groups: vehicle, anti-PD-1, BRAFi+EGFRi, and anti-PD-1+BRAFi+EGFRi. Results: MSI-H BRAF V600E cells exhibited significantly enhanced malignancy. In vivo, MSI-H BRAF V600E tumors displayed profound alterations in the immune microenvironment, including reduced infiltration of CD8⁺ T cells, along with decreased IFN-γ and GZMB levels. Conversely, M2 macrophages were significantly increased. Multiplex immunofluorescence confirmed reduced CD8⁺ T cell infiltration, and elevated PD-1⁺ cell frequencies. Notably, MSI-H BRAF V600E tumors exhibited an increased proportion of PD-1⁺CD8⁺ T cells and greater spatial separation between CD8⁺ T cells and PD-L1⁺ tumor cells. In vivo, combined PD-1, BRAF, and EGFR inhibition resulted in the strongest tumor suppression in MSI-H BRAF V600E tumors, demonstrating a marked therapeutic advantage, including decreased infiltration of CD8⁺ T cells, along with decreased IL-2 and GZMB levels. Conclusions: MSI-H BRAFV600E CRC exhibits distinct molecular and immunological characteristics. Our findings demonstrate that triple-combination therapy targeting PD-1, BRAF, and EGFR substantially enhances antitumor activity in MSI-H BRAFV600E tumors, outperforming ICIs alone or targeted therapy alone. Collectively, these results support a refined molecular subclassification of MSI-H CRC and provide valuable insights for optimizing personalized immunotherapeutic strategies for CRC patients with MSI-H BRAFV600E.

Coordination chemistry presents an ideal molecular platform for the development of superior drug-delivery systems that can be effectively released, selectively targeted, and integrated into functional therapeutic systems. Due to their predictable geometries and tunable bonding properties, metal ions can form a variety of structures, including coordination polymer nanoparticles (CPNs), metal-organic frameworks (MOFs), supramolecular coordination complexes (SCCs), and metal-ligand cross-linked hydrogels. These structures possess a high cargo-loading ability and are sensitive to physiologically significant stimuli, including pH gradients, redox imbalances, enzymatic activity, and light. In addition to drug encapsulation, metal centers are intrinsically imaging-contrastive, catalytic, magnetically responsive, and phototherapeutic, enabling synergistic, multimodal therapies. This review critically analyzes the principles of coordination underlying the rational design of these delivery platforms, the key classes of coordination-based carriers, and their applications in cancer therapy, antimicrobial and antiviral treatment, gene and protein delivery, and theranostics. Emerging trends, such as hybrid organic-inorganic-bimolecular systems, hierarchical self-assembly, and AI-directed design, have also been described as definite areas of transformation in next-generation therapeutics. Issues related to physiological stability, metal toxicity, immune response, and scalable manufacturing are discussed, along with means to support clinical translation. Coordination-based architectures are expected to give the next generation of precise therapeutics that facilitate spectacular regulation of molecular assembly, dynamic reactions, and treatment. Coordination chemistry enables programmable, stimuli-responsive drug delivery. Metal-ligand platforms enable targeted, controlled, and multimodal therapeutics. MOFs, CPNs, SCCs, and hydrogels have high loading and biological responsiveness. Coordination systems combine imaging, therapy, and precision-medicine capabilities. Hybrid architectures promote synergistic, adaptive, and clinically translatable delivery.

This study is a first-in-human, three-stage, phase 1 trial (NCT05154604) designed to evaluate the trophoblast cell-surface antigen 2 (TROP-2)-targeted antibody-drug conjugate SHR-A1921 (1.5-6.0 mg/kg every 3 weeks) in 391 patients with pretreated advanced/metastatic solid tumors. Grade ≥3 treatment-related adverse events occurred in 132 patients (33.8%), with the most common being stomatitis, affecting 57 patients (14.6%). SHR-A1921 showed a low incidence of hematologic toxicities, with only 3.1% of patients experiencing grade ≥3 decreases in neutrophil count. The overall objective response rate was 24.8% (95% confidence interval [CI], 20.6-29.4), ranging from 18.2% to 43.1% across cohorts with platinum-resistant ovarian cancer, triple-negative breast cancer, small-cell lung cancer, non-small cell lung cancer, hormone receptor-positive breast cancer, cervical cancer, and biliary tract cancer. No significant correlation was found between TROP-2 expression and treatment efficacy. In summary, SHR-A1921 exhibited promising antitumor activity and a manageable safety profile, with 3.0 mg/kg every 3 weeks selected for further clinical development.

Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells (APCs). They play pivotal roles in orchestrating innate and adaptive immune responses, particularly in cancer. In tumor-draining lymph nodes (tdLNs), de novo priming occurs, where DCs present antigens to naive T cells, activating them and initiating their clonal expansion. In the tumor microenvironment (TME), intratumoral DCs provide survival or co-stimulatory signals to shape T cell differentiation. However, the scarcity and dysfunctional states of DCs can greatly limit anti-tumor responses, and DCs can even be hijacked by tumor-related factors to promote tumor progression. Therefore, comprehensively understanding the anti- or pro-tumor activities of DCs is crucial. In this review, we discuss the ontogeny of DC lineages and the emerging complexity of intratumoral DCs states. Importantly, we emphasize the significant roles of DCs in priming and sustaining productive T cell anti-tumor immunity. In light of these findings, we also explore promising approaches for targeting DCs to boost anti-tumor immunity and overcome resistance to cancer immunotherapies. We propose that insights into the rational design of DC-based immunotherapeutic strategies against cancer hold immense, underexploited potential.

The therapeutic efficacy of adoptive T cell therapy is largely restricted by reduced viability and dysfunction of CD8+ T cells. Continuous antigen stimulation disrupts the expansion, effector function, and metabolic fitness of CD8+ T cells, leading to their differentiation into an exhausted state within the tumor microenvironment (TME). While the function of the cell cycle negative regulator p16 in senescent cells is well understood, its role in T cell exhaustion remains unclear. In this study, we demonstrated that TCR stimulation of CD8+ T cells rapidly upregulates p16 expression, with its levels positively correlating with TCR affinity. Chronic TCR stimulation further increased p16 expression, leading to CD8+ T cell apoptosis and exhaustion differentiation, without inducing DNA damage or cell senescence. Mechanistic investigations revealed that p16 downregulates mTOR, glycolysis, and oxidative phosphorylation (OXPHOS) associated gene expression, resulting in impaired mitochondrial fitness, reduced T cell viability, and diminished effector function. Furthermore, the deletion of p16 significantly enhances the persistence of CD8+ T cells within tumors and suppresses the terminal exhaustion of tumor-infiltrating T cells. Overall, our findings elucidate how increased p16 expression reshapes T cell intracellular metabolism, drives T cell apoptosis and exhaustion differentiation, and ultimately impairs T cell anti-tumor function.

For colorectal cancer patients, metastasis is a major cause of high mortality and short survival. Precision medicine has led to significant advances in targeted therapy and immunotherapy in the treatment of colorectal cancer, providing more options for patients with mCRC and eventually improving their prognosis. However, the use of these drugs is limited by pre-existing intrinsic resistance mechanisms or the ability of cancer cells to acquire resistance. This report presents a colorectal cancer patient who survived 12 years. After the first palliative resection for descending colon cancer, this patient had experienced local recurrence, splenic and diaphragmatic metastases, splenic fossa and incisional implant metastases, renal metastases, and liver metastases. The patient underwent five surgical resection procedures and benefited from surgery combined with chemotherapy. The disease was initially controlled with first-line treatment when the patient developed liver metastases. After the metastases progressed, next-generation sequencing (NGS) revealed the patient's acquired genomic alternation, BRAF V600E. This case highlights the importance of combining local and systemic therapy and the need to be aware of acquired genomic alternations.

Colorectal cancer is a global health challenge with high morbidity and mortality, but its causative factors remain unclear. In recent years, associations between various dietary patterns and colorectal cancer have been identified, but no studies have examined the association between macro- and micronutrient intake and colorectal cancer. This study analyzed the association between colorectal cancer and dietary intake using the logistic least absolute shrinkage and selection operator (LASSO). The data were derived from national data from the 1999–2010 National Health and Nutrition Examination Survey (NHANES) cycle. These data were further filtered to select those aged 50 years or older who self-reported having colorectal cancer (n = 168) and those who did not self-report having colorectal cancer (n = 649). LASSO regression is a new statistical shrinkage technique based on the R statistical software. In this study, LASSO was used to analyze the association between colorectal cancer and the variables from which the most relevant variables were selected. These variables included currently recognized risk factors for colorectal cancer and nutrients related to dietary intake. Age, sex, and race, which are recognised risk factors, still showed a significant association with colorectal cancer after LASSO regression shrinkage. For dietary intake of macro- and micronutrients, only thiamine (beta = 0.003) and zinc (beta = 0.0007) were positively associated with colorectal cancer. The results suggest that thiamine and zinc may be strongly associated with colorectal cancer. However, the results of the LASSO regression are based on statistically derived propensities and have not been validated by ex vivo experiments.

BRAF non-V600 mutation occupies a relatively small but critical subset in colorectal cancer (CRC). However, little is known about the biological functions and impacts of BRAF class III mutation in CRC. Here, we aim to explore how D594A mutation impacts on biological behaviors and immune related signatures in murine CRC cells. BRAF V600E (class I), G469V (class II) and D594A (class III) mutant cell lines were established based on MC38 cells. The biological behaviors of cells were evaluated in respect of cell growth, cell proliferation, cell apoptosis, cell migration and invasion by the methods of colony-forming assay, CCK-8 assay, Annexin V/PI staining and transwell assay. The concentrations of soluble cytokines were detected by ELISA. The membrane expression of immuno-modulatory molecules and the pattern of tumor infiltrating lymphocyte were evaluated by flow cytometry. The molecular mechanism was explored by RNA sequencing. Immunohistochemistry (IHC) staining was used for the detection of CD8α in tumor tissues. qRT-PCR and western blot were performed to assess the mRNA and protein expression. Anti-PD-L1 treatment and cytokines neutralization experiments were conducted in in vivo models. D594A mutant cells displayed lower grade malignancy characteristics than V600E (class I) and G469V (class II) mutant cells. Meanwhile, D594A mutation led to evident immuno-modulatory features including upregulation of MHC Class I and PD-L1. In vivo experiments displayed that the frequency of infiltrated CD8+ T cells was significantly high within D594A mutant tumors, which may provide potential response to anti-PD-L1 therapy. RNA sequencing analysis showed that D594A mutation led to enhanced expression of ATF3 and THBS1, which thus facilitated CXCL9 and CXCL10 production upon IFN-γ treatment. In addition, CXCL9 or CXCL10 neutralization reduced the infiltration of CD8+ T cells into THBS1-overexpressing tumors. D594A mutant CRC exhibited lower aggressiveness and immune-activated phenotype. ATF3-THBS1-CXCL9/CXCL10 axis mediated functional CD8+ T cells infiltration into the microenvironment of D594A mutant CRC. Our present study is helpful to define this mutation in CRC and provide important insights in designing effective immunotherapeutic strategies in clinic.

BRAF non-V600 mutations are a distinct molecular subset of colorectal cancer (CRC) that has little to no clinical similarity to the BRAF V600 mutations. It is generally considered that the BRAF non-V600 mutations correlate with better survival of CRC patients. In this report, we present an unusual case of that a midlife female patient who was initially diagnosed with stage IIIC colon cancer, and multiple metastases were found 25 months after radical surgery. Next-generation sequencing (NGS) revealed the BRAF p.N581I (c.1742A>T) mutation. She received chemotherapy, targeted therapy, and immunotherapy. However, the disease progressed rapidly with rare metastasis of the bone and cerebellum. This case highlights that the BRAF non-V600 mutations, such as BRAF p.N581I mutant, may lead to resistance to epidermal growth factor receptor (EGFR) inhibitors and result in a rapid course in colorectal cancer. The role of BRAF p.N581I mutation in colorectal cancer demands more attention.

Background:Compared to other subtypes, the CMS4 subtype is associated with lacking of effective treatments and poorer survival rates.Methods:A total of 24 patients with CRC were included in this study. DNA and RNA sequencing were performed to acquire somatic mutations and gene expression, respectively. MATH was used to quantify intratumoral heterogeneity. PPI and survival analyses were performed to identify hub DEGs. Reactome and KEGG analyses were performed to analyze the pathways of mutated or DEGs. Single-sample gene set enrichment analysis and Xcell were used to categorize the infiltration of immune cells.Results:The CMS4 patients had a poorer PFS than CMS2/3. CTNNB1 and CCNE1 were common mutated genes in the CMS4 subtype, which were enriched in Wnt and cell cycle signaling pathways, respectively. The MATH score of CMS4 subtype was lower. SLC17A6 was a hub DEG. M2 macrophages were more infiltrated in the tumor microenvironment of CMS4 subtype. The CMS4 subtype tended to have an immunosuppressive microenvironment.Conclusion:This study suggested new perspectives for exploring therapeutic strategies for the CMS4 subtype CRC.

This study investigated the biological role and mechanism of circMETTL15 in colorectal cancer (CRC). Cancer tissues and matched adjacent normal tissues were collected. CircMETTL15, miR-374a-5p, and ESCO2 levels were detected by RT-qPCR and Western Blot. LoVo cells were selected for loss- and gain-of-function assays and rescue assays. Cell proliferation was detected by CCK-8 and colony formation tests, cell apoptosis and cell cycle were detected by flow cytometry, cell migration and invasion were detected by Transwell assay, and protein expression of ki-67, E-cadherin, N-cadherin, and cleaved caspase-3 was detected by Western blot. Through bioinformatics analysis and verification assays, the targeting relationship between circMETTL15, miR-374a-5p, and ESCO2 was studied. The results suggest that circMETTL15 was a stable circRNA that was highly expressed in CRC tissues and cells and was associated with tumor size, higher TNM staging, and lymph node metastasis in CRC patients. Functionally, knocking down circMETTL15 inhibited the proliferation, migration, invasion, and EMT of LoVo cells, and induced apoptosis. Overexpression of circMETTL15 showed the opposite effect. The effects of knockdown or overexpression of circMETTL15 on the biological behavior of LoVo cells were reversed by knockdown of miR-374a-5p or knockdown of ESCO2, respectively. Mechanistically, circMETTL15 acts as a ceRNA for miR-374a-5p to regulate ESCO2 expression, thereby promoting the biological behavior of LoVo cells. In conclusion, the results of this study reveal the role of circMETTL15 in CRC and the underlying molecular mechanism, which provides potential data support for the development of future CRC drugs.

Colon cancer is the most common malignant tumor in the intestine. Abnormal Carboxylesterases 3 (CES3) expression had been reported to be correlated to multiple tumor progression. However, the association among CES3 expression and prognostic value and immune effects in colonic adenocarcinoma (COAD) were unclear. The transcription and expression data of CES3 and corresponding clinical information was downloaded from The Cancer Genome Atlas (TCGA). The CES3 protein expression and the prognostic value were verified based on tissue microarray data. The Cancer immune group Atlas (TCIA), Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the GSE78220 immunotherapy cohort were used to forecast immunotherapy efficacy. Finally, a prognostic immune signature was constructed and verified. Compared with normal colon tissues, the expression of mRNA and protein levels of CES3 were downregulated in tumor tissues. CES3 expression was associated with TIICs. Hihg-CES3 COAD patients had better efficacy of concurrent immunotherapy. CES3-related immune genes (CRIs) were identified and were then used to construct prognostic immune signature and had been successfully verified in GES39582. CES3 might be a potential immune-related gene and promising prognostic biomarker in COAD.

Background: Breast cancer (BRCA) is the most common malignancy with high heterogeneity in women, and the prognostic prediction for BRCA has remained poor. Ferroptosis, a recently identified iron-dependent form of programmed cell death, plays a significant role in BRCA treatment. Some BRCA cell lines are proven to be sensitive to ferroptosis, and some ferroptosis-related genes have been identified as divers or suppressors in the progress of BRCA. This study aimed to explore the prognostic value of ferroptosis-related genes in BRCA. Methods: A ferroptosis-related gene list, messenger RNA (mRNA) gene expression of BRCA patients, and corresponding clinicopathological data were collected from public databases. The patients of the Cancer Genome Atlas (TCGA) were identified as the training cohort, and the ones of the Gene Expression Omnibus (GEO) were looked as the validation cohort. Univariate Cox regression analysis was utilized to identify prognostic ferroptosis-related genes, and subsequent multivariate analysis further screened out important genes to establish a prognostic model. Receiver operating characteristic (ROC) curves were used to validate the model in both internal and external cohorts. Functional analysis was generated to evaluate the potential correlation between tumor immunity and ferroptosis-related genes in BRCA. Results: A ferroptosis-related gene signature stratifying patients into 2 risk score groups was established based on the TCGA cohort, and validated in the GEO cohort. Patients with lower risk scores had better overall survival (OS) compared to those with higher risk scores (P<0.001, TCGA cohort; P<0.05, GEO cohort). The risk score was independently associated with the OS of BRCA patients (P<0.001, TCGA cohort; P<0.05, GEO cohort). The area under the curves (AUCs) of the model in the training and validation cohorts were all around 0.7. Immune-related biological pathways and immune status were significantly different between the 2 divided risk groups. Conclusions: The novel prognostic model composed of 9 ferroptosis-related genes accurately predicts the survival of BRCA patients. It might provide a new sight for ferroptosis-related BRCA therapy.

Objective Recommendations for surveillance after stereotactic body radiation therapy (SBRT) for early-stage nonsmall cell lung cancer (NSCLC) are not well defined. Recently, PET response criteria in solid tumors (PERCIST) have been proposed as a new standardized method to assess radiotherapeutic response both quantitatively and metabolically. The aim of this study was to evaluate therapeutic response following SBRT in early-stage NSCLC patients by comparing PERCIST with the currently widely used RECIST. Materials and methods Forty-nine patients with early-stage NSCLC who had been prescribed SBRT were studied. Responses of lesion were evaluated using CT and 18F-FDG PET according to the RECIST and PERCIST methods. PET-CT scans were obtained before SBRT and 3–6 months after SBRT. Associations between overall survival (OS) and clinicopathologic results (histology, tumor location, tumor size, lymphatic invasion, clinical stage, and radiotherapeutic responses in RECIST and PERCIST) were statistically analyzed. The median patient follow-up was 30 months. Results Thirteen patients had stage IA, 9 stage IB, 10 stage IIA, and 17 stage IIB biopsy-proven NSCLC. Three-year OS was 79.6%. CT scans indicated three regional recurrences. PET-CT/chest indicated three regional recurrences and distant metastasis. Significant differences were observed in response classification between RECIST and PERCIST (Wilcoxon signed-rank test, P = 0.0041). Univariate analysis showed that clinical stage, RECIST, and PERCIST were significant factors associated with OS, whereas by multivariate analysis PERCIST was the only predictor of OS. SMD, PMD/PMR, and CMR in PERCIST criteria were indicative of a 9.900-fold increase in the risk of OS in early NSCLC patients [risk ratio, 9.900 (95% CI, 1.040–21.591); P = 0.001]. Conclusion RECIST based on the anatomic size reduction rate did not demonstrate the correlation between radiotherapeutic response and prognosis in patients with early-stage NSCLC receiving SBRT. However, PERCIST was shown as the strongest independent predictor of outcomes. PERCIST might be considered more suitable for the evaluation of NSCLC tumor response to SBRT than RECIST.

1Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 3Pancreas Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China

Drug carrier materials need to possess good biological safety. Presently, most biosafety evaluation studies use rodent animal models, including rats and rabbits. However, the cost of raising these animals is relatively high and the experimental period is long. Caenorhabditis elegans(C. elegans) presents an ideal toxicological evaluation model due to its simple structure, easy cultivation, short life cycle, and evolutionary conservation. In this paper, we used C. elegans to test the biological safety of our pH-responsive carrier system(FFPFF self-assembling into a nanosphere structure, FFPFF Nps), which was designed for anti-tumor drug delivery. Our results showed that exposure to high doses of FFPFF Nps did not have a significant impact on the survival rate, growth, development, movement, and reproduction of C. elegans. The preliminary evaluation of the overall biological model of C. elegans shows that FFPFF Nps has good biological safety and warrants further study.