Jing Cai

Background: Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastases poses significant treatment challenges, as first-generation EGFR-tyrosine kinase inhibitors (TKIs) (FGET) show limited CNS efficacy. Although third-generation EGFR-TKIs (TGET) exhibit superior CNS penetration, the optimal choice for first-line treatment remains debated. This meta-analysis aims to resolve this controversy by directly comparing the CNS efficacy of TGET vs. FGET in patients with EGFR-mutant NSCLC and CNS metastases. Methods: A thorough literature search was performed for phase 3 randomized controlled trials (RCTs) comparing TGET and FGET in patients with EGFR-mutated NSCLC and CNS metastases. The primary outcome was CNS-progression-free survival (PFS), and secondary outcomes included overall survival (OS), PFS, CNS response rates, and adverse events (AEs). The study was registered in PROSPERO (ID: CRD42024629581). Results: A total of 5 phase 3 RCTs (AENEAS, FLAURA, FURLONG, IBIO-103, and LASER301) met the inclusion criteria. TGET demonstrated superior efficacy in CNS-PFS [hazard ratio (HR): 0.44 (0.33, 0.58), PConclusions: TGET appeared to be better than FGET for patients with EGFR-mutated NSCLC and CNS metastases, showing improved survival, CNS efficacy, and safety.

Purpose:Pulmonary sarcomatoid carcinoma (PSC) is a highly aggressive and poorly differentiated subtype of non–small cell lung cancer (NSCLC) associated with a poor prognosis. We conducted a prospective, single-arm, phase II trial to evaluate the efficacy and safety of tislelizumab in combination with anlotinib as first-line therapy in patients with advanced PSC.Patients and Methods:Eligible patients with advanced PSC without EGFR or ALK mutations received tislelizumab plus anlotinib as first-line treatment until disease progression or unacceptable toxicities. The primary endpoint was the objective response rate (ORR) assessed per RECIST version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival (OS), and safety.Results:Between August 2021 and June 2025, a total of 29 patients were enrolled, with a median age of 71 years (range: 39–79). Two patients (6.90%) achieved a complete response, and 14 (48.28%) achieved a partial response, yielding an ORR of 55.17% [95% confidence interval (CI), 35.69%–73.55%]. The DCR was 96.55% (95% CI, 82.24%–99.91%). After a median follow-up duration of 16.73 months, the median PFS was 9.40 months (95% CI, 3.67–13.30 months), and the median OS was 14.37 months (95% CI, 9.03–17.50 months). The most common treatment-related adverse events (TRAE) were hyperuricemia and maculopapular rash. Grade 3 to 4 TRAEs occurred in eight patients (27.59%), with no treatment-related deaths reported.Conclusions:The combination of tislelizumab and anlotinib demonstrated promising antitumor activity with a manageable safety profile as first-line therapy in patients with advanced PSC.

Data from the efficacy and safety of tislelizumab plus anlotinib as first-line treatment in advanced pulmonary sarcomatoid carcinoma: a single-arm phase II trial.

Purpose: Pulmonary sarcomatoid carcinoma (PSC) is a highly aggressive and poorly differentiated subtype of non–small cell lung cancer (NSCLC) associated with a poor prognosis. We conducted a prospective, single-arm, phase II trial to evaluate the efficacy and safety of tislelizumab in combination with anlotinib as first-line therapy in patients with advanced PSC. Patients and Methods: Eligible patients with advanced PSC without EGFR or ALK mutations received tislelizumab plus anlotinib as first-line treatment until disease progression or unacceptable toxicities. The primary endpoint was the objective response rate (ORR) assessed per RECIST version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival (OS), and safety. Results: Between August 2021 and June 2025, a total of 29 patients were enrolled, with a median age of 71 years (range: 39–79). Two patients (6.90%) achieved a complete response, and 14 (48.28%) achieved a partial response, yielding an ORR of 55.17% [95% confidence interval (CI), 35.69%–73.55%]. The DCR was 96.55% (95% CI, 82.24%–99.91%). After a median follow-up duration of 16.73 months, the median PFS was 9.40 months (95% CI, 3.67–13.30 months), and the median OS was 14.37 months (95% CI, 9.03–17.50 months). The most common treatment-related adverse events (TRAE) were hyperuricemia and maculopapular rash. Grade 3 to 4 TRAEs occurred in eight patients (27.59%), with no treatment-related deaths reported. Conclusions: The combination of tislelizumab and anlotinib demonstrated promising antitumor activity with a manageable safety profile as first-line therapy in patients with advanced PSC.

Tumor Metabolic Behavior modulates the immunosuppressive microenvironment through multiple pathways, thereby compromising anti-tumor immune responses. To date, there have been limited studies assessing the role of metabolic plasticity or immunometabolism in the tumor microenvironment (TME) during metastasis. Notably, emerging evidence suggests the presence of an immunosuppressive niche in brain metastases. This research aims to delineate distinct metabolic signatures in brain metastatic, investigate the impact of tumor-associated glycolysis on the development of brain metastases in lung adenocarcinoma, and characterize the lactylation regulation in this immunosuppressive microenvironment. The GSE131907 and GSE198291 datasets were retrieved for bioinformatic analysis. Combined with the results of proteomic and transcriptomic sequencing conducted on the lung adenocarcinoma brain metastasis model, differentially expressed signaling pathways were systematically identified through KEGG and GO functional annotations. A multimodal approach encompassing immunohistochemical (IHC) staining, immunofluorescence (IF) imaging, enzyme-linked immunosorbent assay (ELISA) quantification, and co-immunoprecipitation (Co-IP) assays was employed to experimentally validate the characteristics of the immunosuppressive microenvironment and the levels of tumor lactate/lactylation. Rescue experiments were performed by adding a lactylation-specific inhibitor (LDHi) or an H3K18la site-specific inhibitor. Finally, immunohistochemical staining was used to verify the expression level of H3K18la in clinical samples. A total of 86,215 cells were extracted from the GSE131907 dataset, and the metabolic profiles of different cell types were analyzed. The results showed that glycolysis plays a dominant role in tumor cell metabolism. Further analysis revealed that early-stage primary lesions exhibit an inflammatory response signature, while advanced-stage primary lesions and brain metastatic lesions display an immunosuppressive signature. Elevated glycolytic flux showed a significant positive correlation with both the progression of brain metastasis and the immune evasion capacity of brain metastatic lesions. Pathological evaluation of tumor tissues from the LLC-BM (Lewis Lung Cancer Brain Metastasis) model confirmed its immunosuppressive characteristics. Additionally, obvious hypoxia was observed in the tumor tissues, accompanied by intratumoral vascular malformation and dysfunction. Significant lactate accumulation was present in the tumor microenvironment of LLC-BM tumors, and prominent lactylation modifications were detected in the tumor regions. In this model, Rac2 was identified as a potential core mediator of lactylation modification in macrophages, promoting the M2 polarization of macrophages. Meanwhile, CD40, TNFSF13 and CCL22 were identified as key immunoregulatory factors regulated by lactylation signaling. Notably, H3K18la was significantly highly expressed in lung cancer brain metastatic lesion samples. The glycolytic pathway plays a critical role in the metabolic reprogramming of tumor cells during lung adenocarcinoma brain metastasis. Tumor glycolysis is closely associated with lung cancer progression, brain metastasis, and immune evasion. The Rac2 could be affected by lactylation, and then facilitate the formation of an immunosuppressive tumor microenvironment by induce the M2 polarization of macrophages.

Background: Lung adenocarcinoma remains a leading cause of cancer-related mortality worldwide, characterized by high genetic and cellular heterogeneity, especially within the tumor microenvironment. Objective: This study integrates single-cell RNA sequencing (scRNA-seq) with genome-wide association studies (GWAS) using Bayesian deconvolution and machine learning techniques to unravel the genetic and functional complexity of lung adenocarcinoma epithelial cells. Methods: We performed scRNA-seq and GWAS analysis to identify critical cell populations affected by genetic variations. Bayesian deconvolution and machine learning techniques were applied to investigate tumor progression, prognosis, and immune-epithelial cell interactions, particularly focusing on immune checkpoint markers such as PD-L1 and CTLA-4. Results: Our analysis highlights the importance of genes like SLC2A1, which regulates glucose metabolism and correlates with tumor invasiveness and poor prognosis. Immune-epithelial interactions suggest a suppressive tumor microenvironment, potentially hindering immune responses. Additionally, machine learning models identify core prognostic genes such as F12, GOLM1, and S100P, which are significantly associated with patient survival. Conclusions: This comprehensive approach provides novel insights into lung adenocarcinoma biology, emphasizing the role of genetic and immune factors in tumor progression. The findings support the development of personalized therapeutic strategies targeting both tumor cells and the immune microenvironment.

This review article delves into the multifaceted role of lactylation modification in antitumor therapy, revealing the complex interplay between lactylation modification and the tumor microenvironment (TME), metabolic reprogramming, gene expression, and immunotherapy. As an emerging epigenetic modification, lactylation has a significant impact on the metabolic pathways of tumor cells, immune evasion, gene expression regulation, and sensitivity to chemotherapy drugs. Studies have shown that lactylation modification significantly alters the development and therapeutic response of tumors by affecting metabolites in the TME, immune cell functions, and signaling pathways. In the field of immunotherapy, the regulatory role of lactylation modification provides a new perspective and potential targets for tumor treatment, including modulating the sensitivity of tumors to immunotherapy by affecting the expression of immune checkpoint molecules and the infiltration of immune cells. Moreover, research progress on lactylation modification in various types of tumors indicates that it may serve as a biomarker to predict patients' responses to chemotherapy and immunotherapy. Overall, research on lactylation modification provides a theoretical foundation for the development of new tumor treatment strategies and holds promise for improving patient prognosis and quality of life. Future research will further explore the application potential of lactylation modification in tumor therapy and how to improve treatment efficacy by targeting lactylation modification.

Pulverized coal (coal) possesses a layered structure similar to graphite and is a potential reinforcing filler. In this paper, ball milling is used to reduce the particle diameter of coal. The coal is modified with KH‐560 to obtain K‐COAL and prepared K‐COAL/styrene‐butadiene rubber (SBR) composites. In addition, carbon black (CB) is modified to obtain CB‐Si69, K‐COAL and CB‐Si69 are added to SBR in different ratios to prepare COAL/CB/SBR composites. The results show that the addition of K‐COAL can improve the vulcanization performance, thermal stability, and mechanical properties of SBR composites, but the reinforcing effect is weak. In the COAL/CB/SBR composites, the vulcanization and mechanical properties of the composites gradually increase with the increase of CB, while those of the thermal stability decrease. The tensile strength of the 10 phr COAL/30 phr CB/SBR composite is 24.1 MPa, which is elevated by 1105% and 205% compared with the pure SBR and 40 phr K‐COAL/SBR composites, respectively. The composites maintain high elasticity while the tensile strengths are greatly improved, and the mechanical properties are significantly enhanced. In conclusion, this paper provides a reference for the clean utilization of coal and shows new possibilities for finding new fillers to replace CB.

Pyruvate Dehydrogenase Kinase 3 (PDK3) has emerged as a significant player in various cancer types, yet its specific impact on cancers including colon cancer remains ambiguous. Through pan-cancer analysis using TCGA data, we found that the expression of PDK3 and the composition of the immune microenvironment for different tumors were highly heterogeneous across tumors. PDK3 is highly expressed in colorectal cancer and may promote tumor proliferation by activating PI3K-AKT signaling. In addition, we found that PDK3 was able to inhibit tumor antigen presentation signals to suppress immune killing. High PDK3 expression predicts less CD8⁺ T cell infiltration and effector function. Moreover, inhibition of PDK3 expression bolstered CD8⁺ T cell-mediated cytotoxicity CD8⁺ T cell infiltration and activation in vivo. Notably, PDK3 was found to facilitate STAT1 activation and elevate programmed death-ligand 1 (PD-L1) expression in colon cancer cells. Importantly, PDK3 inhibition combination with PD-1 blockade significantly activates the infiltrated CD8⁺ T cells to suppress tumor growth and improves the survival benefit in several murine tumor models. In summary, these findings underscore PDK3’s role in fueling colon cancer growth by orchestrating PI3K-AKT signaling and PD-L1 expression and dampening CD8⁺ T cell function.