PD-1/PD-L1 Inhibitor - Related Adverse Events and Their Management in Breast Cancer

Journal of Cancer, Journal Year: 2024, Volume and Issue: 15(9), P. 2770 - 2787

Published: Jan. 1, 2024

As the positive results of multiple clinical trials were released, Programmed cell death 1 (PD-1) and ligand (PD-L1) inhibitors emerge as focus integrative breast cancer treatment.PD-1/PD-L1 are often used a sequential agent to be combined with other agents such chemotherapeutic agents, targeted radiation therapy.As therapies administered simultaneously or in sequence, they prone variety adverse effects on patients while achieving efficacy.It is challenge for clinicians maintaining balance between immune-related effects(irAEs) treatment efficacy.Previous literatures have paid lots attention caused by immunosuppressive themselves, there dearth research management immune during combination immunotherapy treatments.In this review, we discuss overall incidence irAEs PD-1/PD-L1 various types treatments cancer, including chemotherapy, CTLA-4 inhibitors, therapy, radiotherapy, systematically summarizes each organ-related reaction.It important emphasize that event neurological, hematologic, cardiac toxicity, no alternative but terminate immunotherapy.Thus, seeking more effective strategy irAEs' imminent urged raise awareness reactions.

Language: Английский

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Novel therapeutic strategies and drugs for idiopathic pulmonary fibrosis

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 357(10)

Published: July 3, 2024

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown etiology. Currently, drugs used to treat IPF in clinical practice exhibit severe side effects and limitations. To address these issues, this paper discusses the therapeutic preclinical targeted (such as STAT3 TGF-β/Smad pathway inhibitors, chitinase PI3K phosphodiesterase etc.) natural products on IPF. Through summary current research progress, it found that possess multitarget effects, stable efficacy, low nondrug dependence. Furthermore, we discuss significant prospects product molecules combating by influencing immune system, expecting analytical data will aid development new or investigation active ingredients for potential treatments future.

Language: Английский

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Molecular Pathways in Idiopathic Pulmonary Fibrosis: A Review of Novel Insights for Drug Design

Drug Development Research, Journal Year: 2025, Volume and Issue: 86(3)

Published: April 28, 2025

ABSTRACT Idiopathic pulmonary fibrosis is a progressive, irreversible lung disease of unknown cause, characterized by gradual thickening and scarring tissue, impairing oxygen transfer into the bloodstream. As result, symptoms such as shortness breath, fatigue, persistent dry cough occur. Currently, FDA‐approved antifibrotic agents Pirfenidone Nintedanib can slow progression disease. However, these treatments cannot completely stop loss function do not provide significant improvement in quality life patients. progresses, capacity decreases, breath increases, general health deteriorates significantly. Therefore, new more effective, targeted therapies that halt IPF are urgently needed. This review addresses novel strategies to or disease‐related targeting key mechanisms involved pathogenesis IPF. The molecular structure–activity relationships (SARs) synthesized compounds JAK/STAT, TGF‐β/Smad, Wnt/β‐catenin, PI3K, JNK1, other critical signaling pathways were examined. These approaches have great potential for development potent selective therapeutic treatment insights provided this may contribute future efficient drugs.

Language: Английский

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Inhibitory immune checkpoints suppress the surveillance of senescent cells promoting their accumulation with aging and in age-related diseases

Biogerontology, Journal Year: 2024, Volume and Issue: 25(5), P. 749 - 773

Published: July 1, 2024

Abstract The accumulation of pro-inflammatory senescent cells within tissues is a common hallmark the aging process and many age-related diseases. This modification has been called senescence-associated secretory phenotype (SASP) observed in cultured isolated from aged tissues. Currently, there debate whether should be attributed to increased generation or defect their elimination Emerging studies have revealed that display an expression several inhibitory immune checkpoint ligands, especially those programmed cell death protein-1 (PD-1) ligand-1 (PD-L1) proteins. It known PD-L1 cancer cells, target PD-1 receptor cytotoxic CD8 + T natural killer (NK) disturbing functions, e.g., evoking decline activity promoting exhaustion even apoptosis. An increase level protein was able suppress surveillance inhibit by NK cells. Senescent are express ligands for receptors, i.e., PD-1, LILRB4, NKG2A, TIM-3, SIRPα receptors. Here, I will briefly describe pathways examine these checkpoints could involved evasion with seems plausible enhanced signaling can prevent thus promote process.

Language: Английский

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Single‐cell combined with transcriptome sequencing to explore the molecular mechanism of cell communication in idiopathic pulmonary fibrosis

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(12)

Published: June 1, 2024

Abstract Idiopathic pulmonary fibrosis (IPF) is a common, chronic, and progressive lung disease that severely impacts human health survival. However, the intricate molecular underpinnings of IPF remains elusive. This study aims to delve into nuanced interplay cellular interactions in IPF, thereby laying groundwork for innovative therapeutic approaches clinical field IPF. Sophisticated bioinformatics methods were employed identify crucial biomarkers essential progression The GSE122960 single‐cell dataset was obtained from Gene Expression Omnibus (GEO) compendium, intercellular communication potentialities scrutinized via CellChat. random survival forest paradigm established using GSE70866 dataset. Quintessential genes selected through Kaplan–Meier (KM) curves, while immune infiltration examinations, functional enrichment critiques nomogram paradigms inaugurated. Analysis revealed an intimate potential connections between macrophages various cell types, pinpointing five cardinal influencing trajectory prognosis paradigm, sculpted these seminal genes, exhibits superior predictive prowess. Our research meticulously identified critical confirming their association with prognosis, transcriptional governance Interestingly, we discerned genes' engagement EPITHELIAL_MESENCHYMAL_TRANSITION signalling pathway, which may enhance our understanding complexity

Language: Английский

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Lung Microbiome Intervention Attenuates Herpesvirus-Induced Post-HCT Pulmonary Fibrosis Through PD-L1 Upregulation on Dendritic Cells

Published: July 10, 2024

Abstract Alterations in the lung microbiome frequently accompany adverse pulmonary outcomes. Hematopoietic cell transplantation (HCT) markedly affects corresponding with a high incidence of post-HCT complications. In preclinical mouse model HCT, we observed reduction Lactobacillus johnsonii within following transplantation. Intranasal administration live or heat-killed (HK) L. at low doses reduced gammaherpesvirus-induced fibrosis HCT mice, which IL-17A plays an essential role. HK treatment mice suppressed inflammatory cytokine production by macrophages and decreased Il17a expression T helper 17 (Th17) cells. increased PD-L1 on surface type II conventional dendritic cells (cDC2) vitro bone marrow-derived (BMDCs). -exposed BMDCs also inhibited secretion from co-cultured Th17 PD-1-dependent manner. Notably, when was administered to reconstituted marrow PD-1 knockout (KO) lack mediated response, -mediated negated. Collectively, our findings demonstrate that mitigates herpesvirus-induced modulating cDC2 PD-L1, subsequently suppresses cells, pointing towards potential postbiotic-based strategy for immunomodulation address complications HCT.

Language: Английский

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Identification of PANoptosis-related genes for idiopathic pulmonary fibrosis by machine learning and molecular subtype analysis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 14, 2024

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease characterized by grim prognosis, in which various forms of cell death are significant contributors to its development. The objective this study explore diagnostic biomarkers and molecular subtypes associated with PANoptosis IPF, develop reliable models based on PANoptosis-related mechanisms. peripheral blood transcriptomic data IPF from the Gene Expression Omnibus (GEO) database genes GeneCards were utilized conduct differential gene expression analysis weighted co-expression network (WGCNA), identifying differentially expressed (PDEGs). We yielded 9 PDEGs employed machine learning algorithms identify 3 key for IPF: MMP9, FCMR, NIBAN3. Consensus clustering algorithm was applied recognize two subtypes. Cluster 1 exhibited higher abundance adaptive immune response cells enrichment DNA damage repair-related pathways. 2 greater prevalence innate predominant enhancement pathways related lipid cholesterol metabolism vascular remodeling. Diagnostic developed aid clinical decision-making novel approach diagnosis treatment IPF.

Language: Английский

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Interstitial lung diseases with concomitant lung cancer: a data mining approach revealing a complex condition with gender- and immune-associated specific implications

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 17, 2024

Interstitial lung diseases (ILDs) comprise a family of heterogeneous entities, primarily characterised by chronic scarring the parenchyma. Among ILDs, idiopathic pulmonary fibrosis (IPF) is most common interstitial pneumonitis, associated with progressive functional decline leading to respiratory failure, high symptom burden, and mortality. Notably, incidence cancer (LC) in patients already affected ILDs-mainly IPF-is significantly higher than general population. Moreover, these cases are often neglected deprived active oncologic treatments.

Language: Английский

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