With the continuous development of messenger RNA (mRNA) technology, mRNA-based drugs have shown broad application prospects in recent years. Since mRNA is easy to be degraded and difficult to enter cells directly, the mRNA delivery vectors have always been one of the focuses in the development of mRNA-based drugs. Although lipid nanoparticles (LNPs) have been widely used for the delivery of mRNA, they tend to accumulate in the liver, and repeated administration can easily induce inflammatory response which leads to tissue damage. Compared with LNPs, virus-like particles (VLPs) have the advantages of high biocompatibility and safety, being expected to offer new solutions for mRNA delivery. Based on the practical application requirements, this review summarized the research progress in VLPs according to the mRNA delivery steps: particle assembly, delivery into cells, and intracellular release. We hope to provide a basis and design ideas for the development of new VLPs as delivery vectors, promote the application of VLPs in mRNA delivery, and provide new possibilities for the research and application of mRNA-based therapeutics.
RNA, Messenger/administration & dosage* ; Humans ; Nanoparticles/chemistry* ; Genetic Vectors ; Lipids/chemistry* ; Drug Delivery Systems/methods* ; Virion ; Animals ; Gene Transfer Techniques ; Liposomes

The discovery of anaplastic lymphoma kinase (ALK) tyrosine kinase gene rearrangement mutations in non-small cell lung cancer (NSCLC) has driven continuous advancements in ALK-targeted therapies. The next generation of ALK tyrosine kinase inhibitor, Brigatinib, has demonstrated significant efficacy in patients with ALK-positive NSCLC, offering clinical benefits in deep response of tumor, treatment of brain metastases patients, quality of life, and long-term survival. This review will provide current advancements and exploratory directions for Brigatinib.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Lung Neoplasms/enzymology* ; Pyrimidines/therapeutic use* ; Organophosphorus Compounds/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Stage ⅠB non-small cell lung cancer (NSCLC), a potentially curable malignancy, continues to exhibit a substantial recurrence rate post-surgery. Targeted therapy has significantly improved the prognosis of patients with advanced epidermal growth factor receptor mutation (EGFRm), while the need and optimal timing for adjuvant targeted therapy in epidermal growth factor receptor mutant (EGFRm) stage ⅠB patients remain unclear. This review systematically examines the advancements of adjuvant targeted therapy in stage ⅠB EGFRm NSCLC and critically explores the practical problems in its clinical application. Third-generation targeted agents, such as Osimertinib, have significantly improved disease-free survival in stage ⅠB EGFRm NSCLC according to the seventh edition of the TNM staging system. However, the survival benefits in this population based on the eighth/ninth edition staging systems have yet to be fully validated, and stage ⅠB NSCLC patients exhibit different treatment response patterns. Consequently, current research focuses on high-risk subgroups to optimize treatment outcomes. Major clinical challenges include acquired resistance, determining the optimal treatment timing, and implementing individualized treatment strategies. Future research should concentrate on elucidating the mechanisms of resistance, optimizing treatment timing, establishing precise risk stratification systems, and exploring personalized treatment strategies guided by dynamic monitoring of circulating tumor DNA. This review aims to provide a comprehensive analysis of these key issues and offer a theoretical foundation for optimizing the clinical practice of adjuvant targeted therapy in stage ⅠB NSCLC.

Stage ⅠB non-small cell lung cancer (NSCLC), a potentially curable malignancy, continues to exhibit a substantial recurrence rate post-surgery. Targeted therapy has significantly improved the prognosis of patients with advanced epidermal growth factor receptor mutation (EGFRm), while the need and optimal timing for adjuvant targeted therapy in epidermal growth factor receptor mutant (EGFRm) stage ⅠB patients remain unclear. This review systematically examines the advancements of adjuvant targeted therapy in stage ⅠB EGFRm NSCLC and critically explores the practical problems in its clinical application. Third-generation targeted agents, such as Osimertinib, have significantly improved disease-free survival in stage ⅠB EGFRm NSCLC according to the seventh edition of the TNM staging system. However, the survival benefits in this population based on the eighth/ninth edition staging systems have yet to be fully validated, and stage ⅠB NSCLC patients exhibit different treatment response patterns. Consequently, current research focuses on high-risk subgroups to optimize treatment outcomes. Major clinical challenges include acquired resistance, determining the optimal treatment timing, and implementing individualized treatment strategies. Future research should concentrate on elucidating the mechanisms of resistance, optimizing treatment timing, establishing precise risk stratification systems, and exploring personalized treatment strategies guided by dynamic monitoring of circulating tumor DNA. This review aims to provide a comprehensive analysis of these key issues and offer a theoretical foundation for optimizing the clinical practice of adjuvant targeted therapy in stage ⅠB NSCLC.

Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Objective To investigate the advantages and efficacy of traction with titanium clips in endoscopic submucosal dissection(ESD)for large laterally spreading tumor(LST)in rectum and sigmoid colon.Methods 67 patients with large sigmoid or rectal LST underwent ESD from January 2018 to June 2022 were analyzed retrospectively,including 32 patients in Group A and 35 patients in Group B.Group A was treated with clip-line traction and group B was treated with traditional ESD.The size of lesion,the total operation time,the submucosal dissection time,submucosal dissection rate,submucosal injection number,en bloc resection rate,R0 resection rate,curative resection rate and complications of the two groups were compared.Results LST-G-M was the most common type and villous adenoma was the main pathology in both groups.There were no differences in en bloc resection rate,R0 resection rate and incidence of complications between the two groups.The average size of group A was(13.6±8.4)cm2,significantly larger than that in group B(9.3±4.7)cm2,the total operation time was(42.3±10.3)min in group A,significantly shorter than that in group B(47.9±10.1)min,submucosal dissection time was(30.7±8.2)min in group A,significantly shorter than that in group B(36.1±7.6)min,submucosal injection number was(2.7±1.1)times in group A,significantly less than that in group B(3.5±1.2)times,submucosal dissection rate was(0.4±0.2)cm2/min in group A,significantly faster than that in group B(0.2±0.1)cm2/min,the differences were statistically significant(P<0.05).Conclusion Compared with traditional ESD,clip-line traction can provide a better surgical field and more effective dissection for large LST in rectum and sigmoid colon.

Humans ; Aminoquinolines/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Standard of Care

Lung cancer remains to have the highest morbidity and mortality rates in China among known malignant tumors. Novel drugs and regimens have been sought because of the limited efficiency of traditional chemotherapy and radiotherapy in lung cancer treatment. In the last 20 years, rapid developments in molecular targeted therapy and immunotherapy have increased clinical efficacy and benefitted patients with cancer. Treatments for lung cancer are the most rapidly developed among treatments for solid tumors, pioneering tumor precision medicine. This manuscript reviews the evolution and development of targeted therapy and immunotherapy and discusses existing problems and future directions in the precision therapy of lung cancer.

Monoclonal antibodies have been successfully incorporated into the current therapeutical landscape of lung cancer in the last decades. Recently, with technological advances, bispecific antibodies (bsAbs) have also shown robust efficacy in the treatment of malignant cancers, including lung cancer. These antibodies target two independent epitopes or antigens and have been extensively explored in translational and clinical studies in lung cancer. Here, we outline the mechanisms of action of bsAbs, related clinical data, ongoing clinical trials, and potent novel compounds of various types of bsAbs in clinical studies, especially in lung cancer. We also propose future directions for the clinical development of bsAbs, which might bring a new era of treatment for patients with lung cancer.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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