Small molecule agents for triple negative breast cancer: Current status and future prospects

Translational Oncology, Год журнала: 2024, Номер 41, С. 101893 - 101893

Опубликована: Янв. 29, 2024

Triple-negative breast cancer (TNBC) is a subtype of with poor prognosis. The number cases increased by 2.26 million in 2020, making it the most commonly diagnosed type world. TNBCs lack hormone receptor (HR) and human epidermal growth factor 2 (HER2), which limits treatment options. Currently, paclitaxel-based drugs combined other chemotherapeutics remain main for TNBC. There currently no consensus on best therapeutic regimen However, there have been successful clinical trials exploring large-molecule monoclonal antibodies, small-molecule targeted drugs, novel antibody-drug conjugate (ADC). Although antibodies produced success, their large molecular weight can limit benefits. It worth noting that past 30 years, FDA has approved small molecule HER2-positive cancers. effective targets occurrence drug resistance pose significant challenges To improve prognosis TNBC, crucial to search overcome resistance. This review examines efficacy, adverse effects, mechanisms, potential solutions both monotherapies combination therapies. New targets, including nuclear export protein 1 (XPO1) hedgehog (Hh), are emerging as options researchers become integrated into Additionally, growing interest degradation chimeras (PROTACs), degraders rogue proteins, future therapy direction. provides potentially valuable insights implications.

Язык: Английский

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Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 22, 2024

Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of gastric mucosa. The pathogenesis GC intricately linked to tumor microenvironment within which reside. Tumor-associated macrophages (TAMs) primarily differentiate peripheral blood monocytes and can be broadly categorized into M1 M2 subtypes. M2-type TAMs have been shown promote growth, tissue remodeling, angiogenesis. Furthermore, they actively suppress acquired immunity, leading poorer prognosis reduced tolerance chemotherapy. Exosomes, contain myriad biologically active molecules including lipids, proteins, mRNA, noncoding RNAs, emerged as key mediators communication between TAMs. exchange these via exosomes markedly influence consequently impact progression. Recent studies elucidated correlation various clinicopathological parameters GC, such size, differentiation, infiltration depth, lymph node metastasis, TNM staging, highlighting pivotal role in development metastasis. In this review, we aim comprehensively examine bidirectional TAMs, implications alterations on immune escape, invasion, metastasis targeted therapeutic approaches for efficacy potential drug resistance strategies.

Язык: Английский

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PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 4, 2024

Immunotherapy has been developed, which harnesses and enhances the innate powers of immune system to fight disease, particularly cancer. PD-1 (programmed death-1) PD-L1 death ligand-1) are key components in regulation system, context cancer immunotherapy. regulated by PTMs, including phosphorylation, ubiquitination, deubiquitination, acetylation, palmitoylation glycosylation. PROTACs (Proteolysis Targeting Chimeras) a type new drug design technology. They specifically engineered molecules that target specific proteins within cell for degradation. have designed demonstrated their inhibitory activity against PD-1/PD-L1 pathway, showed ability degrade proteins. In this review, we describe how improve efficacy could be novel strategy combine with radiotherapy, chemotherapy immunotherapy patients.

Язык: Английский

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Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 1, 2024

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and accounts for more than 90% primary liver cancer. The advent immune checkpoint inhibitor (ICI)-related therapies combined with angiogenesis inhibition has revolutionized treatment HCC in late-stage unresectable HCC, as ICIs alone were disappointing treating HCC. In addition to altered microenvironment, abnormal lipid metabolism been extensively characterized various types Stains are known their cholesterol-lowering properties long history hypercholesterolemia reducing cardiovascular disease risk. Apart from ICI other conventional therapies, statins frequently used by advanced patients dyslipidemia, which often marked accumulation cholesterol fatty acids liver. Supported a body preclinical clinical studies, may unexpectedly enhance efficacy therapy through regulation inflammatory responses microenvironment. This review discusses changes summarizes evidence benefits stain use prospects possible mechanistic actions transforming microenvironment when immunotherapies. Consequently, statin emerge novel valuable adjuvant immunotherapies

Язык: Английский

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Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric cancer

World Journal of Gastrointestinal Oncology, Год журнала: 2025, Номер 17(2)

Опубликована: Янв. 18, 2025

Colony-stimulating factor 3 (CSF3) and its receptor (CSF3R) are known to promote gastric cancer (GC) growth metastasis. However, their effects on the immune microenvironment remain unclear. Our analysis indicated a potential link between CSF3R expression immunosuppressive leukocyte immunoglobulin-like B2 (LILRB2) in GC. We hypothesized that CSF3/CSF3R may regulate LILRB2 ligands, angiopoietin-like protein 2 (ANGPTL2) human antigen-G (HLA-G), contributing immunosuppression. To investigate relationship LILRB2, as well ligands ANGPTL2 HLA-G, Transcriptome sequencing data from The Cancer Genome Atlas were analyzed, stratifying patients by expression. Differentially expressed genes checkpoints evaluated. Immunohistochemistry (IHC) was performed GC tissues. Correlation analyses of CSF3R, ANGPTL2, HLA-G conducted using IHC results. cells treated with CSF3, levels measured quantitative reverse transcriptase-polymerase chain reaction western blotting. Among 122 upregulated high groups, showed most significant increase. results (63.0%), (56.5%), (73.9%) Strong positive correlations existed mRNA (P < 0.001). confirmed 0.001), = 0.010), but not > 0.05). CSF3 increased cells. Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered expression, impacting CSF3's regulatory effects. pathway contribute immunosuppression upregulating heterogeneous playing role.

Язык: Английский

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Tumor-derived extracellular vesicle PD-1 promotes tumor immune evasion via disruption of peripheral T cell homeostasis

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217486 - 217486

Опубликована: Янв. 1, 2025

Язык: Английский

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Updated Bayesian network meta-analysis on the efficacy and safety of PD−1 versus PD−L1 inhibitors in first−line treatment with chemotherapy for extensive−stage small-cell lung cancer

Frontiers in Oncology, Год журнала: 2025, Номер 14

Опубликована: Янв. 28, 2025

Objective To compare the efficacy and safety of programmed cell death 1 inhibitors plus chemotherapy (PD-1 + Chemo) ligand (PD-L1 for treatment extensive-stage small-cell lung cancer (ES-SCLC). Methods We performed a meta-analysis relevant data using R software, considering overall survival (OS), progression-free (PFS), grade ≥ 3 treatment-related adverse events (TRAES). Results PD-1 Chemo (OS: hazard ratio [HR] 0.71; PFS: HR 0.59) PD-L1 0.72; 0.73) significantly prolonged did not increase incidence ≥3 TRAEs compared with chemotherapy. Indirect comparisons showed no significant difference in clinical 0.99, 95% CI: 0.86–1.1; 0.80, 0.61–1.0) or (HR 1.0, 0.93–1.1) between Chemo. Non-cumulative probability ranking plot results that ranked first OS PFS. Patients expression levels &lt; 1%, trend disadvantage 1.3; 1.2), whereas patients advantage 0.85; 0.85). Conclusions PFS ES-SCLC TRAES. The profiles appear to be similar.

Язык: Английский

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Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Фев. 26, 2025

Abstract The battle against cancer has evolved over centuries, from the early stages of surgical resection to contemporary treatments including chemotherapy, radiation, targeted therapies, and immunotherapies. Despite significant advances in treatment recent decades, these therapies remain limited by various challenges. Immune checkpoint inhibitors (ICIs), a cornerstone tumor immunotherapy, have emerged as one most promising advancements treatment. Although ICIs, such CTLA-4 PD-1/PD-L1 inhibitors, demonstrated clinical efficacy, their therapeutic impact remains suboptimal due patient-specific variability immune resistance. Cell death is fundamental process for maintaining tissue homeostasis function. Recent research highlights that combination induced regulatory cell (RCD) ICIs can substantially enhance anti-tumor responses across multiple types. In cells exhibiting high levels recombinant solute carrier family 7 member 11 (SLC7A11) protein, glucose deprivation triggers programmed (PCD) pathway characterized disulfide bond formation REDOX (reduction-oxidation) reactions, termed “disulfidptosis.” Studies suggest disulfidptosis plays critical role efficacy SLC7A11 cancers. Therefore, investigate potential synergy between this study will explore mechanisms both processes progression, with goal enhancing response targeting intracellular pathway.

Язык: Английский

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Exploring Immune Checkpoint Inhibitors: Focus on PD-1/PD-L1 Axis and Beyond

Pathology - Research and Practice, Год журнала: 2025, Номер 269, С. 155864 - 155864

Опубликована: Март 1, 2025

Язык: Английский

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Comprehensive immunophenotyping reveals distinct tumor microenvironment alterations in anti-PD-1 sensitive and resistant syngeneic mouse model

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 10, 2025

The advent of immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway has revolutionized cancer treatment, resulting in improved clinical outcomes. However, resistance remains a critical challenge. This study aimed to comparatively elucidate immunophenotypic changes syngeneic mouse models sensitive (MC-38) or resistant (LLC1) anti-PD-1 monoclonal antibody (mAb) treatment. In MC-38 model, therapy increased dendritic cells (DCs) and macrophages, while decreasing myeloid-derived suppressor (MDSCs) within tumor microenvironment. Enhanced expression antigen presentation molecules (MHC I/II) costimulatory (CD80/CD86) was observed on tumor-associated DCs macrophages. Tumor-infiltrating CD4+T, CD8+T, regulatory T, NK, NKT also significantly increased. Importantly, treatment boosted lymphocyte cytotoxic potential, with perforin identified as key marker efficacy. Notably, CD4+T strongly negatively correlated volume. contrast, LLC1 model exhibited minimal upon These findings highlight modifications induced by therapy, particularly role perforin, DC/MDSC ratio predicting therapeutic research offers valuable insights into potential predictive biomarkers informs strategies overcome resistance, emphasizing complex interplay between microenvironment, ultimately aiming improve immunotherapy response rates.

Язык: Английский

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