BACKGROUND: This study aims to compare the efficacy between neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy vs . chemotherapy, and neoadjuvant triplet vs . doublet chemotherapeutic regimens in locally advanced gastric/esophagogastric junction cancer (LAGC). METHODS: We included LAGC patients from 47 hospitals in China's National Cancer Information Database (NCID) from January 2019 to December 2022. Using propensity score matching (PSM), we retrospectively analyzed the efficacy between neoadjuvant ICIs plus chemotherapy vs . chemotherapy alone, and neoadjuvant triplet vs . doublet chemotherapeutic regimens. The primary study result was the pathologic complete response (pCR) rate. The secondary study results were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 1205 LAGC patients were included. After PSM, the ICIs plus chemotherapy and the chemotherapy cohorts had 184 patients each, while the doublet and triplet chemotherapy cohorts had 246 patients each. The pCR rate (14.13% vs . 7.61%, χ2 = 4.039, P = 0.044), and the 2-year (77.60% vs . 61.02%, HR = 0.67, 95% con-fidence interval [CI] 0.43-0.98, P = 0.048) and 3-year (70.55% vs . 61.02%, HR = 0.58, 95% CI 0.32-0.93, P = 0.048) DFS rates in the ICIs plus chemotherapy cohort were improved compared to those in the chemotherapy cohort. No significant increase was observed in the OS rates at both 1 year and 2 years. The pCR rates, DFS rates at 1-3 years, and OS rates at 1-2 years did not differ significantly between the doublet and triplet cohorts, respectively. No differences were observed in postoperative complications between any of the group comparisons. CONCLUSIONS Neoadjuvant ICIs plus chemotherapy improved the pCR rate and 2-3 years DFS rates of LAGC compared to chemotherapy alone, but whether short-term benefit could translate into long-term efficacy is unclear. The triplet regimen was not superior to the doublet regimen in terms of efficacy. The safety after surgery was similar between either ICIs plus chemotherapy and chemotherapy or the triplet and the doublet regimen.
Humans ; Stomach Neoplasms/metabolism* ; Female ; Neoadjuvant Therapy/methods* ; Immune Checkpoint Inhibitors/therapeutic use* ; Male ; Middle Aged ; Propensity Score ; Retrospective Studies ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Disease-Free Survival ; Cohort Studies

Over the past decade,the new cases and deaths of breast cancer has rank first among malignant tumors in women,and its incidence is rising,with a younger age trend.Breast cancer demonstrates a high degree of heterogeneity and is prone to drug re-sistance to comprehensive treatment.As a newly discovered regulatory cell death form mediated by copper,cuproptosis is closely relat-ed to the occurrence and development of breast cancer.With the advancement of nano-medicine,metal-based drugs represented by copper can selectively deliver copper ions to tumor sites through the specific delivery system of nanomaterials.These metal drugs kill tumor cells by inducing copper overload,regulating the tumor microenvironment,and enhancing anti-tumor immune response.There-fore,copper-based drugs exhibit significant application potential in the treatment of breast cancer.This article reviews of the mecha-nism of cuproptosis in the occurrence and development of breast cancer and the application and progress of nanomedicine-mediated cuproptosis in the treatment of breast cancer.

Objective:To investigate the effects of enolase 1(ENO1)on the proliferation,migration,and invasion of gastric cancer cells and its underlying molecular mechanisms.Methods:The expression levels of ENO1 in human gastric cancer cell lines(HGC27,MKN-45,N-87,MGC803,BGC-823)and human gastric mucosal epithelial cells(GES-1)were detected using WB assay.Gene editing tools such as CRISPR and overexpression system were used to construct ENO1 knockdown and knockdown-rescue cell lines.Both MKN-45 and BGC-823 cells were grouped into control(Ctrl)group,ENO1 knockdown(ENO1 KD)group,and ENO1 knockdown-rescue(ENO1 KD-OE)group.The effects of ENO1 knockdown or ENO1 knockdown-rescue on the proliferation,migration,invasion,and apoptosis of gastric cancer cells were evaluated using colony formation assay,EdU staining,scratch wound healing assay,Transwell chamber assay and flow cytometry.Additionally,a xenograft model was established in nude mice,and the effects of ENO1 on tumor growth were monitored using small animal in vivo imaging and tumor tissue block measurement.ENO1 was silenced in MKN-45 cells employing RNA interference technology,and the downstream target genes of ENO1 were identified using RNA co-immunoprecipitation sequencing(RIP-seq)and bioinformatics analysis.The molecular mechanisms by which ENO1 regulates the proliferation,migration and invasion of gastric cancer cells was also analyzed.Results:ENO1 was significantly upregulated in gastric cancer cell lines(P<0.01 or P<0.001).ENO1 knockdown significantly inhibited proliferation,migration,and invasion while promoting apoptosis in MKN-45 and BGC-823 cells(P<0.001,P<0.000 1).Rescue experiments showed that restoring ENO1 expression significantly enhanced cell proliferation,migration,invasion,and inhibited apoptosis(P<0.05,P<0.01,P<0.001,P<0.000 1).In vivo experiments demonstrated that ENO1 knockdown significantly inhibited tumor growth in nude mice(P<0.000 1).The differentially expressed genes interacting with ENO1 protein were primarily enriched in pathways related to RNA splicing.Additionally,ENO1 protein was found to interact with the PKM gene,and their expressions showed a positive correlation in gastric cancer tissues(r=0.886).Conclusion:ENO1 is highly expressed in gastric cancer cells.ENO1 interacts with precursor mRNA of PKM to influence its RNA splicing process,thereby regulating PKM2 expression and promoting gastric cancer progression.

Over the past decade,the new cases and deaths of breast cancer has rank first among malignant tumors in women,and its incidence is rising,with a younger age trend.Breast cancer demonstrates a high degree of heterogeneity and is prone to drug re-sistance to comprehensive treatment.As a newly discovered regulatory cell death form mediated by copper,cuproptosis is closely relat-ed to the occurrence and development of breast cancer.With the advancement of nano-medicine,metal-based drugs represented by copper can selectively deliver copper ions to tumor sites through the specific delivery system of nanomaterials.These metal drugs kill tumor cells by inducing copper overload,regulating the tumor microenvironment,and enhancing anti-tumor immune response.There-fore,copper-based drugs exhibit significant application potential in the treatment of breast cancer.This article reviews of the mecha-nism of cuproptosis in the occurrence and development of breast cancer and the application and progress of nanomedicine-mediated cuproptosis in the treatment of breast cancer.

As a highly heterogeneous disease, breast cancer ranks first in new cases and deaths of female malignant tumors. In recent years, the incidence of breast cancer increases and tends to be younger. Early-onset breast cancer (<40 years old) is mostly associated with adverse biological characteristics and poor prognosis. Although immunotherapy and targeted therapy have advances in the treatment of breast cancer, a major challenge of neoplastic resistance to systemic therapy remains. Therefore, early diagnostic markers and potential therapeutic targets with high specificity and sensitivity must be identified. miR-21 affects the occurrence and development of breast cancer by targeting related genes and regulating related signaling pathways (PTEN/PI3K/Akt and NF-κB/ miR-21-5p/PDCD4 signaling pathways). This paper reviews the mechanism and progress of miR-21 in breast cancer.

Metabolic reprogramming is one of the significant characteristics of malignant tumor development.It provides the tumor with sufficient energy and materials.During the process by which tumor cells acquire metabolic reprogramming,epigenetic changes play a crucial role.N6-methyladenosine(m6A)in mRNA is the most common post-transcriptional modification of mRNA.It regulates the transcription,maturation,translation,and degradation of mRNA.Studies have shown that m6A helps promote the metabolic reprogramming of tumor cells.However,the complete mechanism still requires further research.METTL3 is a key enzyme for m6A methylation that catalyzes m6A progression by forming complexes with other proteins,such as METTL14 and WTAP.Notably,the critical role of METTL3 in the metabolic transition of gastrointestinal tumors has not been given due attention.This article summarizes the specific pathways through which METTL3 affects the reprogramming of cellular glucose metabolism in gastrointestinal tumors.We aimed to clarify the importance of METTL3 in the energy reprogramming of gastrointestinal tumors.

Cancer is a major disease that seriously endangers human health.In recent years,immune checkpoint inhibitors(ICIs)have changed the paradigm of treatment for various solid tumors.Although the initial treatment effect is significant,the issue of drug resistance in this therapy has gradually become apparent.It is particularly important to have a deep understanding of the mecha-nisms of ICIs resistance.Neutrophils in the tumor microenvironment(TME)play a critical role in the resistance of programmed cell death protein-1(PD-1)and its ligand inhibitors.Thus,remodeling tumor-associated neutrophils(TANs)can not only enhance the anti-tumor immune response,but also contribute to improving patient prognosis.This article aims to explore the potential role of TANs in ICIs resistance and summarize current efforts to overcome ICIs resistance.

Cancer is a major disease that seriously endangers human health.In recent years,immune checkpoint inhibitors(ICIs)have changed the paradigm of treatment for various solid tumors.Although the initial treatment effect is significant,the issue of drug resistance in this therapy has gradually become apparent.It is particularly important to have a deep understanding of the mecha-nisms of ICIs resistance.Neutrophils in the tumor microenvironment(TME)play a critical role in the resistance of programmed cell death protein-1(PD-1)and its ligand inhibitors.Thus,remodeling tumor-associated neutrophils(TANs)can not only enhance the anti-tumor immune response,but also contribute to improving patient prognosis.This article aims to explore the potential role of TANs in ICIs resistance and summarize current efforts to overcome ICIs resistance.

Antibody-drug conjugates (ADCs) are novel drugs consisting of monoclonal antibodies targeting tumor-specific or tumor-associated antigens coupled with different numbers of payloads via linkers. ADCs have shown promising clinical benefits in the treatment of a variety of malignancies. Small-cell lung cancer (SCLC) is a hypo-differentiated neuroendocrine tumor with an extremely high degree of malignancy. Although SCLC is sensitive to radiotherapy and chemotherapy, it has a poor prognosis due to characteristics such as early susceptibility to metastasis and recurrence. Progress in the treatment of SCLC is very limited, and more durable and effective therapies should be developed to improve prognosis. However, the progress of SCLC-related therapeutic agents has been limited by the lack of specific molecular targets. This article reviews the basic principles and mechanisms of ADCs, highlights the research progress of relevant drugs against some targets in SCLC, and summarizes new targets that may be developed as targeted drugs.

Immunotherapy for gastric cancer has recently received attention. As a result, the guidelines for diagnosis and treatment of advanced gastric cancer have been revised. Many clinical studies have begun to pay attention to perioperative immunotherapy for gastric cancer. This article discusses the perioperative treatment of gastric cancer in the new era of immunity to contribute to the hot issues in this field.