Stereotactic body radiotherapy (SBRT), also known as stereotatic ablative radiotherapy (SABR), is a non-invasive treatment method that can precisely delivery of ablation radiation dose. After decades of development and refinement, SBRT has been proved to be a safe and effective treatment for early stage non-small cell lung cancer (NSCLC). For patients with early-stage NSCLC who are ineligible or decline surgical intervention, SBRT has emerged as the standard treatment option. Additionally, for patients with early-stage NSCLC who cannot undergo pathological confirmation, SBRT is considered as one of the best choices. Despite the continuous advancements in clinical treatment with SBRT, numerous challenges remain. On one hand, to further enhance the local control rate (LCR) and pathologic complete response (pCR) rate among patients with early-stage NSCLC, scholars are actively exploring the potential of SBRT as a neoadjuvant therapy. On the other hand, despite the high LCR observed in patients with early-stage NSCLC after SBRT, distant metastasis remains a major issue affecting patient prognosis. Consequently, the combination of SBRT with systemic therapy has become a focal point of current research. Furthermore, the radiological changes observed in patients with early-stage NSCLC following SBRT have prompted new considerations in efficacy assessment and differential diagnosis. Therefore, this article delves into the international guidelines for the treatment of early-stage NSCLC, the current treatment landscape, and the clinical challenges and reflections faced, from both clinical and technical perspectives.

Lung cancer is one of the most prevalent and the highest mortality rate malignancies, and its treatment landscape has undergone a disruptive transformation with the discovery and clinical application of immune checkpoint inhibitors. However, there still exists a number of patients who acquire resistance or fail to respond to these treatments, posing new challenges for lung cancer therapy. In light of this, there is an urgent need to actively explore and develop novel targets and innovative therapeutic strategies. This article aims to review the cutting-edge advancements in the novel immune checkpoint inhibitors, agonists, bispecific antibodies, adoptive cellular immunotherapy, and combination therapies involving immune checkpoint inhibitors, as well as to revisit existing related clinical trials along with their limitations, with the goal of advancing lung cancer immunotherapy towards a more personalized and precise approach.

Epidermal growth factor receptor (EGFR) gene mutation is a common oncogenic driver mutation in non-small cell lung cancer (NSCLC). For patients with this gene mutation, the preferred first-line treatment is targeted therapy with an EGFR tyrosine kinase inhibitor, but the issues of drug resistance and disease progression will inevitably arise during the treatment. Standard platinum-based doublet chemotherapy regiment after failure of EGFR-TKIs has limited benefit, and more effective treatment strategies urgently need to be developed. In recent years, many studies have confirmed the efficacy of immunotherapy in NSCLC patients. Nevertheless, for advanced NSCLC patients with EGFR gene mutations, the efficacy of immunotherapy monotherapy is not satisfactory, thus immunotherapy-based combination therapy is receiving increasing attention.

The epidermal growth factor receptor (EGFR) gene is the most common driver gene in non-small cell lung cancer (NSCLC). The third generation tyrosine kinase inhibitor (TKIs) targeting EGFR mutations are the preferred first-line treatment choice for EGFR-mutated advanced NSCLC patients. Although third-generation EGFR-TKIs have provided durable survival benefits for patients, the emergence of drug resistance poses significant challenges for subsequent treatment. Currently, the mechanisms of resistance to the third-generation EGFR-TKIs and corresponding treatment strategies are under investigation. The resistance mechanisms to third-generation EGFR-TKIs can be classified into two types: EGFR-dependent and EGFR-independent. EGFR-dependent resistance mechanisms represent acquired EGFR mutations including C797S. EGFR-independent resistance mechanisms include activation of bypass signaling pathways, alterations in cell cycle-related genes, and phenotypic transformation. Researchers are exploring potential post-resistant treatment approaches such as fourth-generation EGFR-TKIs, combination therapy, chemotherapy, and immunotherapy to overcome these resistance mechanisms. Through in-depth study of resistance mechanisms and the exploration of novel treatment strategies, we hope to overcome the resistance to third-generation EGFR-TKIs, providing more treatment options and better clinical outcomes for EGFR-mutated advanced NSCLC patients.

Objective: To explore the impact of TP53 and RB1 gene mutation status on the efficacy of immunotherapy in patients with extensive-stage small cell lung cancer (SCLC).

Methods: This study retrospectively analyzed the clinical and pathological data of patients with extensive-stage SCLC who received immunotherapy at the department of oncology of Shanghai Chest Hospital from August 2019 to November 2022. A detailed investigation was conducted on patients with next-generation sequencing (NGS) data. By applying Kaplan-Meier survival analysis and COX proportional hazards model, the study evaluated the impact of TP53 and RB1 gene mutation status on the prognosis and clinical significance of patients with extensive-stage SCLC.

Results: A total of 110 patients with extensive-stage SCLC who received immunotherapy and had NGS data were enrolled initially. Based on the TP53 and RB1 gene mutation status, the patients were divided into three groups: TP53/RB1 co-mutation (TP53mut/RB1mut) in 87 cases (79.1%), TP53 mutation/RB1 wild-type (TP53mut/RB1wt) in 20 cases (18.2%), and TP53/RB1 both wild-type (TP53wt/RB1wt) in 3 cases (2.7%). To avoid the influence of a small sample size, the final analysis excluded the 3 patients with TP53/RB1 both wild-type group, and the remaining 107 patients were divided into two groups for further analysis: TP53/RB1 co-mutation group and TP53 mutation/RB1 wild-type group. The study found that compared to TP53/RB1 co-mutation, TP53 mutation/RB1 wild-type significantly shortened the progression-free survival (PFS) (P=0.048) and overall survival (OS) (P=0.027) of patients with extensive-stage SCLC receiving immunotherapy; the results of univariate COX proportional hazards model analysis indicated that TP53 mutation/RB1 wild-type was a prognostic factor for OS in patients with extensive-stage SCLC receiving immunotherapy [ HR=1.827 (95% CI: 1.061-3.149), P=0.030]; the results of multivariate COX proportional hazards model analysis showed that TP53 mutation/RB1 wild-type was an independent risk factor for PFS [HR=1.812 (95% CI: 1.033-3.177), P=0.038], and ECOG PS score ≥1 was an independent risk factor for OS [HR=2.579 (95% CI: 1.073-6.196), P=0.034] in patients with extensive-stage SCLC receiving immunotherapy.

Conclusion: Among the patients with extensive-stage SCLC receiving immunotherapy, patients with TP53 mutation/RB1 wild-type have a worse immunotherapy efficacy and prognosis compared to those with TP53/RB1 co-mutation, and TP53 mutation/RB1 wild-type is an independent risk factor for PFS in patients with extensive-stage SCLC receiving immunotherapy.

Lung cancer has the highest mortality rate in China, even in the world, of which non-small cell lung cancer (NSCLC) is the predominant histological type. Surgery is an important treatment method for patients with stage Ⅰ-ⅢA NSCLC. In recent years, immune checkpoint inhibitors (ICIs) have become a hot research topic in lung cancer research. Multiple clinical studies have shown that preoperative neoadjuvant immunotherapy has a good application prospect in lung cancer, but there are also many problems to be solved. This review summarizes the latest research progress of neoadjuvant immunotherapy for NSCLC, and discusses the challenges and the future development direction.

Lung cancer is the second most common and the deadliest malignant tumor worldwide. With the popularization and improved accuracy of computed tomography (CT) screening technology, more and more patients with lung cancer are detected at an early stage. Concurrently, the rapid development of gene sequencing technology has gradually evolved the treatment model for lung cancer patients into a precision treatment model that integrates pathological classification, staging, and molecular identification. Against this backdrop, targeted drugs such as osimertinib and icotinib have been formally approved for adjuvant therapy after radical resection surgery for resectable non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor(EGFR) mutations, marking the advent of a new era in adjuvant targeted therapy for lung cancer. Despite this significant progress, the optimal perioperative treatment strategies for resectable NSCLC patients with oncogenic driver mutations (including EGFR mutations) are still unclear. To address this issue, multiple clinical trials are currently ongoing. There is increasing attention on neoadjuvant and adjuvant treatment strategies based on targeted therapy (alone or combined with other treatment). These strategies are expected to provide more precise and effective perioperative treatment options for resectable NSCLC patients with EGFR mutations, thereby further improving their prognosis and quality of life.

Brain is one of the most common metastatic sites for lung cancer, and brain metastases seriously affect the clinical prognosis of patients with non-small cell lung cancer (NSCLC). In the era of targeted therapy, a series of tyrosine kinase inhibitors (TKIs) have brought significant survival benefits to patients with NSCLC. However, this has also led to an increasing number of long-term survivors experiencing brain metastases. As a traditional treatment of brain metastases, radiotherapy can effectively control intracranial symptoms and improve the clinical condition of patients. In recent years, with the increased penetration of TKIs into the central nervous system, the intracranial control of NSCLC patients with brain metastases receiving TKI treatment has significantly improved, and the role of radiotherapy in patients with brain metastases has been gradually challenged. Therefore, how to rationally choose TKIs and radiotherapy to treat NSCLC brain metastases has become an important issue that needs to be addressed urgently.

Objective: To evaluate the associations of exposures in early-life with the risk of colorectal cancer (CRC) using the UK Biobank (UKB) data.

Methods: A total of 462 253 participants from the UKB were included in this analysis. For each subject, self-reported exposures in early-life from the baseline data collected in 2006–2010, which included maternal smoking, single or multiple birth, birth weight, breastfeed as baby, comparative body size and height at age 10, relative age of first facial hair (for males) and age at menarche (for females), were extracted. The incident cases of CRC and all-cause deaths during the follow-up period up to December 31, 2021 were further obtained. COX proportional hazards regression models were applied to evaluate the hazard ratio (HR) and 95% confidence interval (CI) of early-life exposures with the risk of CRC after adjusting for age, gender, race family history of CRC, body mass index, family income, and education level at baseline.

Results: After adjustment for potential confounding, high birth weight (> 4 kg), breastfeed as baby, comparative height at 10 (shorter) and relative age at first facial hair (later) were associated with the risk of CRC, with an HR (95% CI) of 1.14 (1.03-1.25), 1.33 (1.24-1.43), 0.92 (0.85-0.98) and 0.80 (0.76-0.95), respectively. Several associations were found to be modified by lifestyle factors in adulthood.

Conclusion: Our results indicated that the exposures in early-life, especially during adolescence, may contribute to the development of CRC. These results help to better understand the etiology and mechanisms of CRC, and provide evidence for decision making in CRC prevention.

Cancer is one of the most serious public health issues globally and a leading cause of death among residents in China. Among various types of cancer, lung cancer has the highest incidence and mortality rates, posing a significant challenge to Chinese healthcare system. Currently, comprehensive treatment of lung cancer is thrivig, but surgical remains the primary curative treatment. The advent of surgical robots has opened up new possibilities for the surgical treatment of lung cancer. With flexibility, precision, minimally invasive nature, and intelligence, robotic surgery has addressed many challenges and shortcomings of traditional surgical treatments, representing a revolutionary achievement in the integration of medicine and engineering. As the installation and utilization of surgical robots rapidly increase, the prospects and potential risks of robotic surgery for lung cancer have garnered widespread attention. Looking ahead, new concepts and technologies, including artificial intelligence, remote control, haptic feedback, etc., are expected to be implemented in robots for a further optimized lung cancer surgical process. This integration will influence the landscape of lung cancer surgical treatment, and ultimately benefit patients.

In January 2024, professor Shen Baiyong's team at the Pancreas Center-Shanghai Key Laboratory of Translational Research in Pancreatic Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, published a research paper in Nature Medicine titled “Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma”. The team conducted a prospective observational study that included a total of 1 171 pancreatic cancer patients who underwent radical resection. First, paired samples of tumors from 191 pancreatic ductal adenocarcinoma (PDAC) patients were obtained by microdissection and subjected to proteomic analysis, which revealed unique protein modules of pancreatic tumors, particularly those related to chemotherapeutic drug sensitivity. Further, the research team established a prognostic risk model for pancreatic cancer at the proteomic level and validated the validity and reliability of this prognostic model with an external cohort. Using multicenter and large sample data, the study constructed and validated the generalizability of two protein markers in predicting the efficacy of chemotherapy in pancreatic tumors.

Objective: This study aimed to investigate the correlation between the use of glucose-lowering drugs and the risk of pancreatic cancer through propensity score matching (PSM), which provides a scientific basis for clinical decision-making.

Methods: This study retrospectively analyzed the clinical data of patients diagnosed with type 2 diabetes mellitus (T2DM) and treated with glucose-lowering drugs in Nanjing Drum Tower Hospital between 2000 and 2023. The patients were divided into two groups: those with T2DM alone and those with T2DM combined with pancreatic cancer. PSM was employed to align the baseline characteristics of patients across groups, minimizing the impact of confounding factors. According to the use of glucose-lowering drugs, the correlation between the use of various types of glucose-lowering drugs and the occurrence of pancreatic cancer was explored by logistic regression analysis, and the drug influencing factors that might potentially affect the occurrence of pancreatic cancer were screened out. Additionally, the relationship between the use of glucose-lowering medications, both as monotherapy and in combination, and the occurrence of pancreatic cancer was further analyzed.

Results: The logistic regression analyses showed that previous use of sulfonylureas was significantly associated with pancreatic cancer in patients with T2DM, and previous use of dipeptidyl peptidase-4 (DPP-4) inhibitors was weakly associated with pancreatic cancer, and sulfonylureas [odds ratio (OR)=0.631，95% CI: 0.415-0.961，P=0.032] and dipeptidyl peptidase-4 (DPP-4) inhibitors (OR=0.639，95% CI: 0.388-1.052，P=0.078) may be associated with a reduced risk of pancreatic cancer in T2DM patients. Other drugs, including insulin, metformin, α-glucosidase inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors, were not significantly associated with pancreatic cancer development. In a further analysis of glucose-lowering treatment regimens, it was shown that metformin in combination with other oral glucose-lowering agents was associated with pancreatic cancer [adjustment OR (aOR)=0.463， 95% CI：0.224-0.959， P=0.038] and may be a protective factor for pancreatic carcinogenesis.

Conclusion: The use of sulfonylureas and DPP-4 inhibitors in T2DM patients is related to the reduction of pancreatic cancer, and compared with the use of drugs alone, the use of drugs combined with oral hypoglycemic drugs can further reduce the incidence of pancreatic cancer.

Objective: To investigate the effect of de novo designed epidermal growth factor receptor (EGFR) binding protein EGn and fibroblast growth factor receptor (FGFR) Ⅲ c binding protein FG2 on pancreatic cancer cells.

Methods: EGn and FG2 sequences were obtained from an existing study, and the proteins were amplified and expressed in Escherichia coli BL21(DE3) followed by purification through Ni-NTA affinity chromatography and size exclusion chromatography. The purified protein was tested with SDS-PAGE followed by Coomassie Brilliant Blue staining for purity evaluation. The expression level of EGFR and FGFR2 Ⅲc in PANC-1, MIA PaCa-2 and BxPC-3 cells was compared using Western blotting and real-time fluorescence quantitative PCR. The binding of EGn and FG2 in different pancreatic cancer cell lines was assessed by flow cytometry. The effect of EGn and FG2 on the phosphorylation of the target receptors or the down-stream extracellular signal-regulated kinase (ERK) molecules was analyzed by Western blotting. The effect of EGn and FG2 on the proliferation of PANC-1 and MIA PaCa-2 cells was evaluated by CCK-8 assay and colony formation assay. The effect of EGn and FG2 on the migration of PANC-1 cells was examined by Transwell assay.

Results: EGn and FG2 proteins were successfully purified and can specifically bind to pancreatic cancer cell lines expressing target receptors, with the binding efficiency positively correlated with target receptor expression levels. EGn and FG2 can competitively inhibit the down-stream signaling of target receptors in PANC-1 cells, and significantly suppress the proliferation and migration of PANC-1 cells (P < 0.05). However, their inhibitory effects on the down-stream signaling or proliferation in MIA PaCa-1 and BxPC-3 cells were relatively limited.

Conclusion: EGn and FG2 demonstrate inhibitory effects on the proliferation and migration of PANC-1 cells with high expression of EGFR and ectopic high-expression of FGFR2 Ⅲc, indicating their potential therapeutic efficacy in pancreatic cancer and supporting the potential application of de novo designed binding proteins in targeted therapy for pancreatic cancer.

Lung cancer has become one of the most serious diseases threatening human society. According to statistics, the incidence and mortality rates of lung cancer rank first among all malignant tumors worldwide. Moreover, with the popularization of low-dose CT and other examination methods, more and more patients with lung cancer are detected in the early phase of the tumor. At present, lobectomy with systematic lymph node dissection (SLND) remains the standard treatment for patients with resectable lung cancer. However, in recent years, some studies have shown uncertain survival benefits of SLND for early-stage lung cancer. Instead, SLND was related to the incidence of postoperative complications and decreased immunotherapy efficiency. Therefore, in the treatment of early-stage lung cancer, selective lymph node resection, including mediastinal lymph node sampling (MLNS) and lobe-specific lymph node dissection (L-SLND), are increasingly gaining the attention and acceptance of clinicians. Selective lymph node dissection not only minimizes over-treatment and ensures treatment effectiveness but also reflects a precise understanding of the personalized treatment needs of patients with early-stage lung cancer.

Small-cell lung cancer (SCLC) is a refractory disease. Traditional chemotherapy and radiotherapy are the main treatment approaches, but these approaches are limited in improving the survival rate of the patients. In recent years, with a deeper understanding of the biological characteristics, preclinical laboratory study has provided multiple potential treatment avenues for patients with SCLC. The development of innovative anti-tumor drugs has moved SCLC treatment from the laboratory to the clinic, significantly changing clinical treatment model for SCLC patients. Immune checkpoint inhibitors (ICIs), novel chemotherapeutic agents, and anti-angiogenic agents have established a new standard of SCLC treatment. New targets such as B7H3 and DLL3 have also shown a good application prospect in SCLC treatment, but the further validation of these studies are still needed. In addition, there are still multiple targets under development in the SCLC field, including that this will bring more treatment options for patients with SCLC. Looking to the future, precision treatment strategies based on molecular subtypes are expected to open new treatment prospects for SCLC patients.

Objective: To screen out nociceptive neuron-related genes associated with the prognosis of lung adenocarcinoma (LUAD) patients through bioinformatics analysis and construct a prognostic risk assessment model for LUAD based on these genes, as well as to further explore the correlation between this model and tumor immune microenvironment of LUAD patients.

Methods: Differentially expressed genes between LUAD tumor tissues and normal lung tissues were obtained from the TCGA database, and compared with 117 known nociceptive neuron-related genes to screen out candidate genes significantly associated with the prognosis of LUAD patients. The Lasso algorithm was used to refine the candidate genes to obtain key genes for constructing the LUAD prognostic risk assessment model. Based on this model, LUAD patients in the TCGA database were divided into high-risk and low-risk groups according to the median of the prognostic risk score. The specificity and sensitivity of the model were assessed using the receiver operating characteristic (ROC) curve, and the external dataset GSE31210 was used to verify the effectiveness of this model in predicting the prognosis of LUAD patients. Additionally, univariate and multivariate COX regression analyses were conducted to compare the independent predictive value of the model and clinical parameters for the prognosis of LUAD patients. Finally, immune infiltration analysis was performed to compare the differences in immune function between high-risk and low-risk LUAD patients, further revealing the potential link between nociceptive neuron-related genes and tumor immunity.

Results: A prognostic risk assessment model for LUIAD patients based on 14 nociceptive neuron-related genes was successfully constructed, which was effective in predicting the prognosis of LUAD patients (P<0.001). Further analysis revealed that tumor immune cell infiltration in high-risk LUAD patients was significantly lower than that in low-risk LUAD patients.

Conclusion: This study confirms a significant association between nociceptive neuron-related genes and LUAD, and suggesting that injury stimulation can affect LUAD progression by mediating changes in the tumor immune microenvironment. This finding provides a favorable theoretical support for the development of nociceptive neurons and their receptors as future drug targets for LUAD.

Multiple pulmonary ground-glass nodules (GGNs) constitute the primary radiological hallmark of early-stage lung cancer, and their prevalence has exhibited a noteworthy upward trajectory in recent years. Even following surgical excision of the primary lesion, 21% of the patients manifest secondary primary lung cancers within two years postoperatively. This, compounded by compromised lung function, engenders substantial challenges in facilitating subsequent surgical interventions. Consequently, the vanguard of research within the domain of lung cancer prevention and treatment revolves around realizing minimally invasive local curative modalities for early-stage lung cancer and enhancing secondary cancer prevention. In 2022, the "Expert Consensus on Integrated Traditional Chinese and Western Medicine Approaches to the Prevention and Treatment of Multiple Pulmonary Ground-Glass Nodules" introduced a pioneering diagnostic and therapeutic scheme denoted as Ablation and Mitochondrial Therapy with Traditional Chinese Medicine (AMTC). This seminal contribution furnished a crucial theoretical and practical underpinning for the integrated diagnostic and therapeutic approaches involving both traditional Chinese and Western medicine in the management of pulmonary GGN. Over the preceding two years, noteworthy strides have been accomplished in the application of traditional Chinese medicine to the prevention and treatment of lung cancer. The AMTC integrated diagnostic and therapeutic technology has matured significantly. In light of these developments, The Lung Cancer Integrated Prevention and Screening Special Committee of the Chinese Anti-Cancer Association and the Shanghai Medical Association Integrative Medicine Branch have undertaken a revision of the preceding consensus. This updated consensus introduces standards for the innovative AMTC diagnostic and therapeutic approach, systematically elucidates the novel theory concerning the collaborative restoration of damaged mitochondria through the synergy of traditional Chinese and Western medicine, as well as the clinical innovation referred to as "precision ablation in Western medicine + systematic mitochondrial restoration in traditional Chinese medicine." Furthermore, it outlines a fresh strategy for non-surgical management of early-stage lung cancer while concurrently mitigating the potential progression of nodular malignancies. This strategy effectively materializes secondary cancer prevention and leads to a substantial reduction in the incidence of lung cancer. The release of this consensus is poised to foster the high-quality evolution of integrated traditional Chinese and Western medicine in diagnosis and treatment, elevate the standards of lung cancer prevention and treatment, and provide a robust response to the "Healthy China" initiative, which addresses the pressing healthcare demands of the populace.

The incidence of cachexia in pancreatic cancer is high, which seriously affects the therapeutic effect and survival rate of patients. There is currently no effective intervention for tumor cachexia, so studying its regulatory mechanism has important clinical significance. In 2024, Professor Li Min's team from the Health Science Center of the University of Oklahoma published a research report on Cancer Cell entitled "The crosstalk between macroscopic and cancer cells potentials pancreatic cancer cachexia", which first revealed the relationship between the immune microenvironment (macrophages) of pancreatic cancer and the body's macro environment cachexia (muscle atrophy), opening up a new direction and new intervention ideas for the study of pancreatic cancer cachexia.

Pancreatic cancer has an insidious onset and a high degree of malignancy, and due to the limited efficacy of traditional treatments such as surgery and chemotherapy, this tumor has been one of the malignant tumors with the highest morbidity and mortality rates. In recent years, cell therapy, which utilizes and modifies the patient's own immune cells to target and kill tumor cells, is gradually becoming one of the potential alternatives to traditional treatment of tumors, and has achieved positive results in hematologic tumors. However, cell therapy in solid tumors, such as pancreatic cancer, is still in the research stage, and although it has achieved some efficacy, it is still full of challenges. In this review, the mechanism of chimeric antigen receptor-T cells (CAR-T), T cell receptor-T cells (TCR-T), and tumor infiltrating lymphocytes (TILs) in cell therapy and the efficacy in the treatment of pancreatic cancer were thoroughly discussed. Meanwhile, the main reasons for the poor effect of cell therapy in pancreatic cancer and the current research progress in improving the effect of cell therapy are preliminarily analyzed.

Craniopharyngioma is a rare benign intracranial tumor, and surgical removal is the primary treatment modality. However, due to the deep location of the tumor, its close relationship with the optic nerve, hypothalamic-pituitary axis and essential tissue and vascular structures, and its local invasiveness, treatment still poses numerous challenges. In recent years, there have been advancements in treating craniopharyngioma, including improvements in surgical techniques, equipment, and strategies such as neuroendoscopy, the introduction of novel treatment modalities such as targeted therapies, etc. This paper provides a comprehensive review of these developments.

Objective: To establish a BGJ398-resistant orthotopic model of intrahepatic cholangiocarcinoma (ICC) in mice that simulates the fibroblast growth factor receptor 2 (FGFR2) gene rearrangement/fusion mutations and FGFR2 kinase domain mutations in clinical patients, in order to provide a tool for relavant research.

Methods: Modified FGFR2 gene encoding FGFR2 protein that’s prone to phosphorylation activation was introduced into the mouse liver using hydrodynamic tail vein injection technology to establish a BGJ398-sensitive orthotopic model of ICC. Plasmids injected include pT3-myr-AKT-HA, pT3-EF1a-NICD1, pCMV（CAT）T7-SB100 and pSB[Exp]-myr-FGFR2-FLAG. Then, the mice were treated with BGJ398 for 4 weeks to induce resistance to BGJ398. Ultrasound imaging was used to monitor bile duct obstruction lesions in the model mice in order to access the extent of resistance to BGJ398. HE staining and oil red O staining were used to analyze liver tissue sections for the histological features of the BGJ398-resistant orthotopic ICC model. Immunofluorescence staining was used to analyze the origin of the ICC cells from BGJ398-resistant mice. Primary tumor cells were extracted from the model mice and CCK-8 assay was performed to analyze their sensitivity to BGJ398 in vitro as well as the median inhibition concentration (IC₅₀) of BGJ398. The model mice were treated with BGJ398 and the survival curves were plotted to verify the resistance of the ICC mouse model to drug treatment in vivo. DNA was extracted from drug-resistant ICC tissues and genomic resequencing was used to verify mutations in the kinase domain of the FGFR2 sequence.

Results: The successful rate of the BGJ398-resistant orthotopic ICC mouse model construction was 93.33%, with significant tumor burden observed in the liver. Histologically, ICC tumor tissue was arranged in glandular duct patterns in the liver. Large numbers of lipid droplet vacuoles appeared in HE staining and oil red O staining. Immunofluorescence staining of the liver tissue showed positive results for biliary epithelial cell marker cytokeratin 19 (CK19) and negative results for hepatocyte marker albumin (ALB). Primary ICC tumor cells were extracted and cultured, and CCK-8 results showed that the IC₅₀ value for BGJ398 was 95.22 nmol in BGJ398-sensitive cells while the number increased to 348.4 nmol in BGJ398-resistant cells. After treatment with BGJ398 through intraperitoneal injection, the survival rate for BGJ398-resistnat mice was significantly lower than that of BGJ398-sensitive mice (P = 0.001 7). Subsequent genomic resequencing revealed significant mutations in the FGFR2 gene, verifying that the mutations in the orthotopic ICC mouse model was consistent with those found in clinical ICC patients.

Conclusion: This study has successfully established a BGJ398-resistant orthotopic ICC mouse model, providing valuable tools for further exploration of the molecular mechanisms of resistance to FGFR inhibitors and the development of new treatment methods.

As one of traditional local treatments, photodynamic therapy (PDT) has mainly been used for the local eradicate and palliative treatment of malignant tumors. However, in recent years, more and more evidence has revealed a role of PDT in anti-tumor immunity, which attacked attention from researchers again. PDT can induce the immunogenic death of tumor cells as well as activation of both innate and adaptive immune systems, resulting in the enhancement of immune response against tumors. This article reviewed the advances regarding PDT and tumor immunity, aiming to systematically clarify the role of PDT in anti-tumor immunity and its potential applications in immunotherapy.

Uveal melanoma originates from the uveal tract and has a significant tendency to liver metastasis. Once metastasis occurs, the prognosis is poor. The current treatment options for uveal melanoma are liver-directed therapies including liver partial resection, ablation, isolated hepatic perfusion and percutaneous hepatic perfusion, hepatic artery infusion chemotherapy, transcatheter arterial chemoembolization, immune embolization, and radioembolization, and systemic treatment for metastatic uveal melanoma. This review discusses the pathogenesis of liver metastasis in uveal melanoma and reviews the current treatment options for uveal melanoma.

Objective: To investigate the role of RASAL2 in vasculogenic mimicry in pancreatic cancer cells and to preliminarily explore the potential molecular mechanisms involved.

Methods: The clinical proteomic tumor analysis consortium (CPTAC) database was used to analyze the expression of RASAL2 in pancreatic cancer, and immunohistochemical method was used to detect the expression of RASAL2, β-catenin and Vimentin in pancreatic cancer and adjacent tissues. In the pancreatic cancer cell line, after lentivirus infection knockdown and overexpression of RASAL2, transcriptome sequencing was performed on pancreatic cancer cells silencing RASAL2 expression, and vasculogenic mimicry experiment was used to detect the effect of RASAL2 on angiogenesis of pancreatic cancer cells; The molecular mechanism of RASAL2 promoting vasculogenic mimicry in pancreatic cancer was studied by real-time fluorescent quantitative PCR and Western blotting detection.

Results: The analysis results of CPTAC database showed that the expression level of RASAL2 protein in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue. Immunohistochemical test results showed that the expression of RASAL2 in pancreatic cancer tissue was up-regulated, and the expression of β-catenin and Vimentin in pancreatic cancer tissue was also significantly up-regulated. The second-generation transcriptome sequencing results showed that RASAL2 may be involved in the biological behavior of intercellular connections and adhesion. After knocking down RASAL2 expression in pancreatic cancer cell PANC-1, the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins decreased, and the formation of vasculogenic mimicry structure was inhibited; After overexpression of RASAL2 in pancreatic cancer cell BxPC-3, the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins increased, promoting the formation of vasculogenic mimicry.

Conclusion: The effect of RASAL2 on vasculogenic mimicry in pancreatic cancer cells is related to AKT/β-catenin signaling pathway.

Pancreatic fibrosis is an important pathological feature of pancreatic cancer and chronic pancreatitis, and plays an important role in the progression of pancreatic cancer and chronic pancreatitis. Pancreatic fibrosis blocks the chemotherapy drugs from reaching the cancer cells to do their job and also affects the stiffness of the pancreatic tissue. Therefore, it is important to assess the degree of pancreatic fibrosis as an adjunct to surgical and chemotherapeutic treatments for pancreatic cancer and chronic pancreatitis. In recent years, there have been new research advances and technological breakthroughs in non-invasive diagnostic methods for pancreatic fibrosis. The fields of CT, ultrasound elastography and magnetic resonance imaging have extended new imaging techniques, yielded new imaging indices to assess the degree of pancreatic fibrosis. In this paper, we have collected relevant literatures since 2018 to describe the research progress related to non-invasive diagnostic methods for pancreatic fibrosis.

Paraganglioma (PGL) is a neuroendocrine tumor, which can be divided into extradrenal paraganglioma and intradrenal paraganglioma according to its location. Together they are called PPGL(pheochromocytoma and paraganglioma). With the further study of its molecular biology, PPGL can be divided into three subtypes: pseudohypoxia-driven type, kinase pathway altered type and Wnt pathway altered type. Different subtypes of PPGL can provide different individualized treatments. In this paper, we review the recent advances in different molecular typing and individualized therapy of PPGL.

Pancreatic cancer is a highly malignant digestive system tumor with poor prognosis. Its incidence is closely related to the level of regional development. Epidemiology shows that with the progress of urbanization, the proportion of obese people in the world is increasing over the years. Meanwhile, obesity has also been found to be one of the risk factors for pancreatic cancer. However, the mechanism of obesity regulating pancreatic cancer is still unclear at present. Researches show that obese people with pancreatic cancers have different tumor pathological mechanisms and higher risk of surgical complications. Therefore, this article will review the potential transformation mechanism between microscopic pathological changes and clinical manifestations of obesity related pancreatic cancer.

Pancreatic cancer is a malignant tumor with extremely poor prognosis, and its biological behavior is closely related to its genetic characteristics. Traditional preclinical research models struggle to accurately simulate the complex genetic heterogeneity and histological characteristics of pancreatic cancer. In recent years, the development of organoid models and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology has provided new tools for pancreatic cancer research. Organoids can simulate the genetic and histological features of primary tumors, while CRISPR technology enables precise genetic manipulation in organoids. CRISPR Gene-Editing Organoids can model the occurrence and evolution of pancreatic cancer, conduct gene function analysis, and perform drug screening. This review discusses the recent advancements in the application of organoid models combined with CRISPR technology in pancreatic cancer research, which are expanding our understanding of pancreatic cancer.

Objective: To explore whether anlotinib or bevacizumab has better efficacy in patients with recurrent glioblastoma.

Methods: The clinical characteristics and treatment data of patients with recurrent glioblastoma admitted to Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, were collected retrospectively. All patients received maximal resection of the tumor combined with postoperative adjuvant radiotherapy and chemotherapy, and the recurrence was detected by head contrast-enhanced MRI. According to the choice of anti-vascular therapy, the patients were divided into anlotinib group and bevacizumab group. Survival curves were drawn to compare the overall survival time of the two groups of patients, and subgroup analysis was performed according to the basic information of the patients and whether they received temozolomide chemotherapy or radiotherapy after recurrence.

Results: A total of 37 patients were enrolled in the study, 19 in the anlotinib group and 18 in the bevacizumab group. The median overall survival time was 16.3 months, with 19.6 months in the anlotinib group and 12.8 months in the bevacizumab group. However, survival analysis showed that there was no significant difference in survival time between the anlotinib group and the bevacizumab group (P＝0.88). Further subgroup analysis showed that there was no significant difference in survival time between the two groups in all subgroups.

Conclusion: This study provided an initial indication of the efficacy of anlotinib in patients with recurrent glioblastoma and suggested that oral anlotinib may be a viable option for patients who were unable to tolerate bevacizumab or who had.

Objective: To analyze the effect of perineural invasion (PNI) on immune cell infiltration in pancreatic ductal adenocarcinoma (PDAC) by the CIBERSORT deconvolution algorithm.

Methods: The pancreatic cancer patients from the dataset GSE102238 were re-evaluated for the severity of PNI. And then the high and low PNI subgroups were subjected to immune scoring and immune cell infiltration analysis using the ESTIMATE and CIBERSORT algorithms to find immune cell subgroups associated with PNI. Finally, the results were validated by tissue microarrays.

Results: Twenty-five cases were selected from 50 pancreatic cancer specimens for PNI reassessment and then divided into two high and low groups. Compared to the low PNI group, specimens from patients in the high group showed significantly less CD8⁺ T-cell infiltration (P<0.05) and significantly more resting memory CD4⁺ T-cells and M0 macrophages (P<0.05). Significantly reduced CD8⁺ T cells (P<0.01) and slightly increased CD4⁺ T cells (P<0.05) were confirmed in the patients with the high PNI using tissue microarrays. Meanwhile, macrophages significantly increased in the high PNI group(P<0.001).

Conclusion: High PNI in PDAC inhibits infiltration of CD8⁺ T cells which promote the infiltration of macrophages.

Objective: To investigate mechanisms whereby phospholipase D1 (PLD1) promotes pancreatic ductal adenocarcinoma (PDAC) progression.

Methods: Targets were identified by screening the Genomic Spatial Event (GSE) database for genes differentially expressed in metastatic and primary tumors. Xenograft models were constructed by orthotopic injection of KPC cells into the mouse pancreas. Differential PLD1 expression in paired primary tumors and liver metastases derived from C57 mice and PDAC patients was confirmed using immunohistochemical staining. The effect of PLD1 expression on PDAC prognosis was assessed using a PDAC tissue microarray and clinical data. The effect of PLD1 expression on PDAC metastasis was assessed using transwell migration and scratch assays of cell lines ectopically expressing/silencing PLD1. The role of PLD1 in tumor metastasis was investigated using xenograft models constructed by orthotopic injection of PLD1-overexpression cell lines or vector control into the pancreas of C57 mice. Growth of primary tumors and liver metastases was monitored using bioluminescent imaging. The role of PLD1 in tumor progression was assessed using western blotting, transwell migration and scratch assays, and PLD1 enzyme-mutation cell lines. Downstream PLD1 target genes were identified using quantitative real-time PCR (qPCR), transcriptome sequencing, and response blocking. The effect of downstream target FSTL1 on liver metastasis in mice was assessed using bioluminescent imaging.

Results: PLD1 expression was significantly higher in metastases than in primary tumors in KPC mice and patients.In the tissue microarray analysis, PLD1 expression was associated with diminished survival in PDAC patients; PLD1 overexpression in MIA PaCa-2 cells or knockdown in SW1990 cells could significantly affect the ability of invasion and migration.Xenograft models were established via orthotopic injections of the KPC cell line into the pancreas.Bioluminescent imaging demonstrated that PLD1 overexpression significantly increased signal intensity in the mouse liver (P<0.01);Treating the SW1990 cell line with PA and choline (PLD1 pathway products) did not restore loss of PDAC cell migration and invasion ability. Transwell and scratch assays in KRM, a PLD1 catalytic-mutation cell line, suggested that PLD1 activity is not required for PDAC metastasis;Transcriptome sequencing identified FSTL1 as a downstream molecule of PLD1. qPCR confirmed the consistency of mRNA levels between PLD1 and FSTL1. A blocking-rescue experiment suggested that FSTL1 is a downstream target of PLD1. A splenectomy metastasis model was constructed by injecting nude mice with tumor cells overexpressing FSTL1 and the results confirmed that overexpression of FSTL1 could induce liver metastases in PDAC cell due to tumor progression.

Conclusion: PLD1 upregulates FSTL1 expression, promotes epithelial-mesenchymal transition of tumor cells, and enhances PDAC metastasis. Thus, PLD1 blockade could inhibit PDAC progression.

Objective: To investigate the effect of copper chlorophyllin sodium salt (CHL) on the sensitivity of human pancreatic cancer cells in response to gemcitabine (GEM) therapy and on the therapeutic effect on pancreatic cancer cells that have developed GEM resistance.

Methods: MIA GR (a pancreatic cancer cell line resistant to GEM) was induced by a low-dose continuous incremental method, and the half inhibitory concentration (IC₅₀) of MIA WT and MIA GR to GEM treatment was detected by the CCK-8 method, and the resistance index was calculated; the difference in IC₅₀ of CHL on the two types of cells was detected by the CCK-8 method after treating MIA WT and MIA GR cells with different concentrations of CHL, CCK-8 method was used to detect the difference in IC₅₀ of CHL on the two types of cells; on the basis of IC₅₀, MIA WT and MIA GR cells were intervened with CHL and (or) GEM with different multiplicity of IC₅₀, respectively, and the growth inhibition curves of MIA WT and MIA GR cells were detected by the CCK-8 method under the intervention of CHL combined with GEM; After the intervention of MIA WT and MIA GR cells with CHL and (or) GEM at IC₅₀, respectively, the effects on the proliferation of the two different cells were detected using the clone formation assay; the effects on cytotoxicity/activity were observed under fluorescence microscopy; and the effects on apoptosis were detected using flow cytometry. Finally, western blotting was used to detect the effects of CHL and (or) GEM interventions on the drug resistance-associated molecules P-glycoprotein (P-gp) and ribonucleotide reductase regulatory subunit M2 (RRM2) in MIA GR cells, the and sensitivity-related molecule deoxycytidine kinase (DCK) on protein expression levels.

Results: MIA GR cells were verified to be well drug resistant, with resistance indices of 549.1 and 667.9 after 48 h and 96 h after GEM intervention compared to homologous wild-type MIA WT cells, respectively; CHL intervention inhibited the proliferation of MIA GR cells more significantly compared to that of MIA WT cells; and CHL in combination with GEM exerted a more significant growth inhibitory effect compared to GEM alone in both MIA WT cells (P<0.001) and MIA GR cells (P<0.01). CHL significantly inhibited the tumor proliferation of MIA GR cells, and the inhibitory effect was more pronounced in both cells when combined with GEM (P < 0.000 1); furthermore, compared to GEM alone, the intervention with CHL could cause more pronounced cytotoxicity (P < 0.000 1) in both MIA WT and MIA GR cells. caused more pronounced cytotoxicity (P < 0.000 1) and induced a higher percentage of apoptosis than GEM alone. The results of the western blotting assay showed that CHL intervention caused a decrease in the expression levels of P-gp and RRM2 proteins, as well as an increase in the protein expression level of DCK in MIA GR cells.

Conclusion: CHL increases the sensitivity of pancreatic cancer cells to GEM and also induces a decrease in the resistance of drug-resistant pancreatic cancer cells to GEM.

In 2024, Xue Jing's research team from Shanghai Jiao Tong University School of Medicine published a research paper in the journal Cancer Cell titled “Tumor Cell inflammatory dysregulation shapes cancer associated fibroblasts heterogeneity to metabolically support pancreatic cancer”. Studies have found that deletion of the tumor-intrinsic SET domain containing 2 (SETD2) releases bone morphogenetic protein 2 (BMP2) signals through abnormal increases in H3K27Ac, leading to the differentiation of cancer-associated fibroblasts (CAFs) cells toward a lipid-rich phenotype. Lipid-rich CAFs cells provide lipids to tumor cells through the ABCA8a transporter and enhance mitochondrial oxidative phosphorylation metabolism. Taken together, this study links epigenetic dysregulation of CAFs cells to tumor cells and highlights previously unrecognized metabolic crosstalk between CAFs cells and pancreatic tumor cells. In addition, the study also proposed using oxidative phosphorylation as a potential strategy for targeted treatment of patients with SETD2-deficient pancreatic ductal adenocarcinoma, providing new ideas for precise diagnosis and treatment.

As a real-time, rapid and non-invasive method for monitoring the occurrence and development of various diseases and evaluating the health status of the body, breath detection has attracted wide attention in the application of early lung cancer screening. However, there is significant variability in the reported specific biomarkers of lung cancer, making it difficult to reach a unified consensus. Meanwhile, the pathways for the generation of volatile organic compounds (VOCs) in exhaled breath of lung cancer patients remain unclear, and further research on the detailed metabolic mechanisms is required. Therefore, this review comprehensively summarizes the VOCs detected in the exhaled breath of lung cancer patients from relevant literature in the past five years, deeply analyzes the production mechanism of these VOCs and the internal correlation with the disease, and evaluates the performance of the lung cancer prediction models constructed based on these VOCs, in order to provide reference for clinical and subsequent researches.

Meningioma is the most common type of primary intracranial tumor and includes grade I, II and III by the world health organization (WHO) classification in 2021. With the increase of grade, the higher the recurrence rate of tumor, the worse the prognosis. Surgery is the main treatment, and radiotherapy is used for residual or recurrent tumors. However, some patients often lost the opportunity of surgery and radiotherapy who recurred after multiple surgeries or radiotherapy. Medical treatment is limited. Therefore, effective treatment is an urgent problem to be solved. In recent years, immunotherapy has achieved good efficacy in a variety of malignant tumors. Meningioma also harbors abundant immune microenvironment basing on the large of evidence of genome and infiltrated immune cells of meningioma, immunotherapy may be a choice for the treatment of recurrent or refractory meningioma. This article mainly reviews the components of the immune microenvironment in meningioma and the progress of immunotherapy, and summarizes the expression and application of immune checkpoint proteins in the meningioma in the past years, aiming to find out effective immune targets for clinical transformation and bring new hope for meningioma patients.

The rapid development of the comprehensive intersection of oncology disciplines makes oncology teaching complex and challenging. In recent years, the deep integration of artificial intelligence (AI) and medical education has brought new opportunities for oncology teaching. Therefore, this paper proposes to construct a new teaching model of AI-enabled problem-based learning (PBL) fused with case-based learning (CBL), which fully combines PBL, CBL, virtual simulation technology, intelligent robots, AI models and other teaching methods, and integrates these innovative elements into all aspects of oncology teaching, including theoretical courses, laboratory operations and clinical practice, in order to provide a comprehensive and interactive oncology teaching system. This new teaching mode brings a new perspective and approach to theoretical, experimental, and clinical teaching in oncology, which not only helps to deepen students’ understanding of the basics of oncology, but also significantly improves their clinical thinking and problem-solving abilities. In addition, this new attempt at an integrated teaching method will provide a new teaching strategy for the development of medical oncology education.

Objective: This study aims to construct a human peripheral blood mononuclear cell (PBMC)-NPSG-PDX (patient-derived xenograft) model, by transferring PBMCs into NPSG (NOD-Prkdc^scidIl2rg^null/Shjh) mice and transplanting human tumor tissues. This model mimics the human tumor microenvironment to investigate the interactions between tumors and the immune system.

Methods: PBMCs from healthy donors were transferred to NPSG mice to generate hPBMC-NPSG model. Patient-derived xenografts (PDX) were established in nude (BALB/c-nu) mice. Third-generation PDX tumors were then transplanted into hPBMC-NPSG mice to establish the hPBMC-NPSG-PDX model. Mouse body weight was monitored, and flow cytometry was used to analyze immune reconstitution and T cell function. Tumor growth was evaluated, and immunohistochemistry was performed to analyze tumor morphology and immune cell infiltration.

Results: Fourteen days after constructing the hPBMC-NPSG mouse model, the proportion of human hu-CD45⁺CD3⁺ T cells reached 97%. The proportions of human CD8⁺ T, CD4⁺ T, CD56⁺ natural killer (NK), and CD19⁺ B cells were 64%, 24%, 4.6%, and 1.0%, respectively. Human CD4⁺ and CD8⁺ cells secreted various cytokines (IL-2, IFN-γ, and TNF-α) and expressed cytotoxic molecules (FasL, granzyme B, and perforin) 28 days post reconstitution. Tumor growth in hPBMC-NPSG-PDX mice was rapid initially but then stabilized. Immunohistochemistry staining revealed typical tumor morphology, and tumor cell apoptosis was observed in areas with immune cell infiltration.

Conclusion: This study successfully constructed a hPBMC-NPSG-PDX model that effectively simulates the human tumor microenvironment, providing an ideal platform for tumor immunology research.

Ferroptosis is a form of iron dependent cell death, which is closely related to the progress and prognosis of bladder cancer (BCa). Among them, erroptosis related genes (FRGs) play an important role in the biological effects of BCa, such as participating in regulating the proliferation, migration, metastasis, drug resistance, immune regulation, and therapeutic efficacy of BCa cells. In addition, FRGs are also important biomarkers for predicting the prognosis of tumor patients. However, the specific mechanism of action of FRGs in BCa remains elusive. How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage. Therefore, exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa. This article aims to systematically elucidate the role of FRGs in the occurrence, development, treatment, and prognosis of BCa. To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients, and constructing prognostic risk prediction models.

Glioma is the most common primary malignant neoplasm of the central nervous system, of which with the poor prognosis for its refractory to all kind of therapy, and new methods are urgently need for clinical glioma treatment. Immunotherapy is a new milestone in tumor treatment, which showed effective results in a variety of solid tumors. At present, the basic research and clinical trials of immunotherapy in glioma are also become hot topics. This article reviews the current status and progress of glioma immunotherapy for better understand the efficacy and limitations of these therapeutic methods, aims to provide new immunotherapy strategies for glioma.

The incidence and mortality rates of gastrointestinal tumors account for 26% and 35% of global malignant tumors, respectively, and continue to rise annually. Elucidating the molecular mechanisms of occurrence and development of gastrointestinal tumors, as well as establishing precise molecularly targeted intervention strategies, have become critical scientific challenges in oncology research. Doublecortin-like kinase 1 (DCLK1), a type II transmembrane protein harboring serine/threonine kinase domains, is well-recognized as a specific molecular marker for cancer stem cells. DCLK1 has been demonstrated to directly promote tumor progression by enhancing the autonomous malignant phenotype of tumor cells, while also indirectly driving tumorigenesis through modulation of tumor immune microenvironment. In recent years, tissue-resident memory T cells (TRM), characterized by their sustained tissue residency and potent antitumor immune efficacy, have emerged as a novel avenue for cancer immunotherapy. This article systematically reviews the molecular regulatory mechanisms of DCLK1 in gastrointestinal tumors, with a focus on its potential association with TRM cell functional activation, aiming to provide a theoretical foundation for DCLK1-targeted inhibitors or monoclonal antibody-based immunotherapeutic strategies.