Single-cell and spatial transcriptomics analysis of non-small cell lung cancer DOI Creative Commons
Marco De Zuani, Haoliang Xue, Jun Sung Park

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 23, 2024

Abstract Lung cancer is the second most frequently diagnosed and leading cause of cancer-related mortality worldwide. Tumour ecosystems feature diverse immune cell types. Myeloid cells, in particular, are prevalent have a well-established role promoting disease. In our study, we profile approximately 900,000 cells from 25 treatment-naive patients with adenocarcinoma squamous-cell carcinoma by single-cell spatial transcriptomics. We note an inverse relationship between anti-inflammatory macrophages NK cells/T reduced cytotoxicity within tumour. While observe similar type composition both carcinoma, detect significant differences co-expression various checkpoint inhibitors. Moreover, reveal evidence transcriptional “reprogramming” tumours, shifting them towards cholesterol export adopting foetal-like signature which promotes iron efflux. Our multi-omic resource offers high-resolution molecular map tumour-associated macrophages, enhancing understanding their tumour microenvironment.

Language: Английский

Impact of Proton Pump Inhibitors and Histamine-2-Receptor Antagonists on Non-Small Cell Lung Cancer Immunotherapy: A Systematic Review and Meta-Analysis DOI Open Access
Alessandro Rizzo, Antonio Cusmai,

Francesco Giovannelli

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(6), P. 1404 - 1404

Published: March 9, 2022

(1) Background: In recent years, immunotherapy has revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), representing a therapeutic breakthrough in this field. Antacid agents such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are commonly prescribed for extended periods NSCLC patients, these drugs have potential to modify efficacy immune checkpoint (ICIs). (2) Materials Methods: Herein, we conducted systematic review meta-analysis investigate impact PPIs H2RAs on progression-free survival (PFS) overall (OS) among patients receiving metastatic NSCLC. Effect measures OS were Hazard Ratios (HRs) 95% Confidence Intervals (CIs), which extracted from available studies. Forest plots used assess HRs describe relationship between specified cohorts patients. (3) Results: Six studies included analysis, involving 2267 The pooled PFS 1.4 (95% CI, 1.25-1.58) 1.29 1.17-1.43), respectively, suggesting that administration was negatively associated with OS. (4) Conclusion: Concomitant antacid use could activity ICIs

Language: Английский

Citations

92
Notch signaling pathway in cancer: from mechanistic insights to targeted therapies DOI Creative Commons

Qingmiao Shi,

Chen Xue,

Yifan Zeng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 27, 2024

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The receptor ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical signaling transduction. Accumulating evidence indicates that the pathway serves as both an oncogenic factor a tumor suppressor various cancer types. Dysregulation of this promotes epithelial-mesenchymal transition angiogenesis malignancies, closely linked proliferation, invasion, metastasis. Furthermore, contributes maintaining stem-like properties cells, thereby enhancing invasiveness. regulatory metabolic reprogramming microenvironment suggests pivotal involvement balancing suppressive effects. Moreover, implicated conferring chemoresistance cells. Therefore, comprehensive understanding these biological processes crucial developing innovative therapeutic strategies targeting signaling. This review focuses on research progress cancers, providing in-depth insights into potential mechanisms regulation occurrence progression cancer. Additionally, summarizes pharmaceutical clinical trials therapy, aiming offer new human malignancies.

Language: Английский

Citations

81
Current advance of nanotechnology in diagnosis and treatment for malignant tumors DOI Creative Commons

Bilan Wang,

Shiqi Hu, Yan Teng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 12, 2024

Cancer remains a significant risk to human health. Nanomedicine is new multidisciplinary field that garnering lot of interest and investigation. shows great potential for cancer diagnosis treatment. Specifically engineered nanoparticles can be employed as contrast agents in diagnostics enable high sensitivity high-resolution tumor detection by imaging examinations. Novel approaches labeling are also made possible the use nanoprobes nanobiosensors. The achievement targeted medication delivery therapy accomplished through rational design manufacture nanodrug carriers. Nanoparticles have capability effectively transport medications or gene fragments tissues via passive active targeting processes, thus enhancing treatment outcomes while minimizing harm healthy tissues. Simultaneously, context radiation sensitization photothermal enhance therapeutic efficacy malignant tumors. This review presents literature overview summary how nanotechnology used According oncological diseases originating from different systems body combining pathophysiological features cancers at sites, we most recent developments applications. Finally, briefly discuss prospects challenges cancer.

Language: Английский

Citations

81
The mechanism of ferroptosis and its related diseases DOI Creative Commons
Shijian Feng, Dan Tang, Yichang Wang

et al.

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

Citations

62
The Significance of SPP1 in Lung Cancers and Its Impact as a Marker for Protumor Tumor-Associated Macrophages DOI Open Access
Eri Matsubara, Hiromu Yano, Cheng Pan

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2250 - 2250

Published: April 12, 2023

Macrophages are a representative cell type in the tumor microenvironment. that infiltrate cancer microenvironment referred to as tumor-associated macrophages (TAMs). TAMs exhibit protumor functions related invasion, metastasis, and immunosuppression, an increased density of is associated with poor clinical course many cancers. Phosphoprotein 1 (SPP1), also known osteopontin, multifunctional secreted phosphorylated glycoprotein. Although SPP1 produced variety organs, at cellular level, it expressed on only few types, such osteoblasts, fibroblasts, macrophages, dendritic cells, lymphoid mononuclear cells. by previous studies have demonstrated correlations between levels circulating and/or expression cells prognosis types cancer. We recently revealed correlated chemoresistance lung adenocarcinoma. In this review, we summarize significance cancers discuss importance new marker for subpopulation monocyte-derived Several shown SPP1/CD44 axis contribute solid cancers, so may represent one most critical mechanisms cell-to-cell communication TAMs.

Language: Английский

Citations

60
A novel signature predicts prognosis and immunotherapy in lung adenocarcinoma based on cancer-associated fibroblasts DOI Creative Commons

Qianhe Ren,

Pengpeng Zhang, Haoran Lin

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 31, 2023

Background Extensive research has established the significant correlations between cancer-associated fibroblasts (CAFs) and various stages of cancer development, including initiation, angiogenesis, progression, resistance to therapy. In this study, we aimed investigate characteristics CAFs in lung adenocarcinoma (LUAD) develop a risk signature predict prognosis patients with LUAD. Methods We obtained single-cell RNA sequencing (scRNA-seq) bulk RNA-seq data from public database. The Seurat R package was used process scRNA-seq identify CAF clusters based on several biomarkers. CAF-related prognostic genes were further identified using univariate Cox regression analysis. To reduce number genes, Lasso performed, established. A novel nomogram that incorporated clinicopathological features developed clinical applicability model. Additionally, conducted immune landscape immunotherapy responsiveness analyses. Finally, performed vitro experiments verify functions EXO1 Results 5 LUAD data, which 3 significantly associated total 492 found be linked 1731 DEGs construct signature. Moreover, our exploration revealed related scores, its ability confirmed. Furthermore, incorporating showed excellent applicability. verified EXP1 through experiments. Conclusions proven an predictor prognosis, stratifying more appropriately precisely predicting responsiveness. comprehensive characterization can response immunotherapy, thus offering fresh perspectives into management patients. Our study ultimately confirms role facilitating invasion growth tumor cells Nevertheless, validation achieved by conducting vivo

Language: Английский

Citations

52
Nanoparticles advanced from preclinical studies to clinical trials for lung cancer therapy DOI Creative Commons
Yifan Liu,

Wenxu Cheng,

HongYi Xin

et al.

Cancer Nanotechnology, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 28, 2023

Abstract Lung cancer is the leading cause of mortality. As a heterogeneous disease, it has different subtypes and various treatment modalities. In addition to conventional surgery, radiotherapy chemotherapy, targeted therapy immunotherapy have also been applied in clinics. However, drug resistance systemic toxicity still cannot be avoided. Based on unique properties nanoparticles, provides new idea for lung therapy, especially immunotherapy. When nanoparticles are used as carriers drugs with special physical properties, nanodrug delivery system ensures accuracy targeting stability while increasing permeability aggregation tumor tissues, showing good anti-tumor effects. This review introduces including polymer liposome quantum dots, dendrimers, gold their applications tissues. addition, specific application nanoparticle-based preclinical studies clinical trials discussed.

Language: Английский

Citations

51
Prospects, advances and biological applications of MOF-based platform for the treatment of lung cancer DOI

Yijun Deng,

Manli Guo,

Luyi Zhou

et al.

Biomaterials Science, Journal Year: 2024, Volume and Issue: 12(15), P. 3725 - 3744

Published: Jan. 1, 2024

Herein, we reviewed the recent development in use of MOF materials as a platform for treatment lung cancer.

Language: Английский

Citations

50
New Horizons in Lung Cancer Management Through ATR/CHK1 Pathway Modulation DOI
Riya Thapa, Obaid Afzal, Asif Ahmad Bhat

et al.

Future Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 15(19), P. 1807 - 1818

Published: Oct. 1, 2023

Lung cancer is the leading cause of cancer-related deaths worldwide. Molecular profiling has contributed to a new classification lung cancer, driving advancements in research and therapy. The ataxia telangiectasia rad3/checkpoint kinase 1 (ATR/CHK1) pathway plays crucial role maintaining genomic stability, its activation been linked development drug resistance poor prognosis. Clinical preclinical studies have demonstrated promising results targeting this pathway. ATR CHK1 are proteins that collaborate repair DNA damage caused by radiation or chemotherapy. ATR/CHK1 inhibitors currently under investigation clinical trials. This article explores potential for treating cancer.

Language: Английский

Citations

48
Exploiting the therapeutic implications of KRAS inhibition on tumor immunity DOI Creative Commons
Míriam Molina‐Arcas, Julian Downward

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(3), P. 338 - 357

Published: March 1, 2024

SummaryOver the past decade, RAS oncogenic proteins have transitioned from being deemed undruggable to having two clinically approved drugs, with several more in advanced stages of development. Despite initial benefit KRAS-G12C inhibitors for patients tumors harboring this mutation, rapid emergence drug resistance underscores urgent need synergize these other therapeutic approaches improve outcomes. mutant tumor cells can create an immunosuppressive microenvironment (TME), suggesting increased susceptibility immunotherapies following inhibition. This provides a rationale combining inhibitory drugs immune checkpoint blockade (ICB). However, achieving synergy clinical setting has proven challenging. Here, we explore how understanding impact on TME guide innovative inhibition immunotherapies, review progress both pre-clinical and stages, discuss challenges future directions.

Language: Английский

Citations

47