Immune Checkpoint Inhibitors in Cancer Therapy

Current Oncology, Journal Year: 2022, Volume and Issue: 29(5), P. 3044 - 3060

Published: April 24, 2022

The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these have been utilized successfully patients with metastatic melanoma, renal cell carcinoma, head neck cancers non-small lung cancer. US FDA has approved three different categories inhibitors (ICIs) PD-1 (Nivolumab, Pembrolizumab, Cemiplimab), PDL-1 (Atezolimumab, Durvalumab Avelumab), inhibitor (Ipilimumab). Unfortunately, not all respond favourably to drugs, highlighting role biomarkers Tumour mutation burden (TMB), expression, microbiome, hypoxia, interferon-γ, ECM predicting responses ICIs-based current study aims review literature updates on ICIs therapy.

Language: Английский

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Integration of clinical features and deep learning on pathology for the prediction of breast cancer recurrence assays and risk of recurrence

npj Breast Cancer, Journal Year: 2023, Volume and Issue: 9(1)

Published: April 14, 2023

Gene expression-based recurrence assays are strongly recommended to guide the use of chemotherapy in hormone receptor-positive, HER2-negative breast cancer, but such testing is expensive, can contribute delays care, and may not be available low-resource settings. Here, we describe training independent validation a deep learning model that predicts assay result risk using both digital histology clinical factors. We demonstrate this approach outperforms an established nomogram (area under receiver operating characteristic curve 0.83 versus 0.76 external cohort, p = 0.0005) identify subset patients with excellent prognoses who need further genomic testing.

Language: Английский

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Immune checkpoint inhibitors associated cardiovascular immune-related adverse events

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 5, 2024

Immune checkpoint inhibitors (ICIs) are specialized monoclonal antibodies (mAbs) that target immune checkpoints and their ligands, counteracting cancer cell-induced T-cell suppression. Approved ICIs like cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), its ligand PD-L1, lymphocyte activation gene-3 (LAG-3) have improved patient outcomes by enhancing anti-tumor responses. However, some patients unresponsive, others experience immune-related adverse events (irAEs), affecting organs the lung, liver, intestine, skin now cardiovascular system. These cardiac irAEs include conditions myocarditis, atherosclerosis, pericarditis, arrhythmias, cardiomyopathy. Ongoing clinical trials investigate promising alternative co-inhibitory receptor targets, including T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) immunoreceptor with ITIM domain (TIGIT). This review delves into mechanisms of approved (CTLA-4, PD-1, LAG-3) upcoming options Tim-3 TIGIT. It explores use in treatment, supported both preclinical data. Additionally, it examines behind toxic irAEs, focusing on ICI-associated myocarditis atherosclerosis. insights vital as continue to revolutionize therapy, offering hope patients, while also necessitating careful monitoring management potential side effects, emerging complications.

Language: Английский

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Exploiting pancreatic cancer metabolism: challenges and opportunities

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(6), P. 592 - 604

Published: April 10, 2024

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer, known for its challenging diagnosis and limited treatment options. The focus on metabolic reprogramming as key factor in tumor initiation, progression, therapy resistance has gained prominence. In this review we the impact changes interplay among stromal, immune, cells, glutamine branched-chain amino acids (BCAAs) emerge pivotal players modulating immune cell functions growth. We also discuss ongoing clinical trials that explore modulation PDAC, targeting mitochondrial metabolism, asparagine addiction, autophagy inhibition. Overcoming challenges understanding nutrient effects immune-stromal-tumor interactions holds promise innovative therapeutic strategies.

Language: Английский

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Prevalence of aggressive care among patients with cancer near the end of life: a systematic review and meta-analysis

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 71, P. 102561 - 102561

Published: March 21, 2024

Aggressive care near patients' end-of-life (EOL) entails limited therapeutic values, high costs, and compromised quality of life (QoL). In this study, we aimed to estimate the global prevalence aggressive in patients with cancer explore potential subgroup differences.

Language: Английский

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A comprehensive review of immune checkpoint inhibitors for cancer treatment

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113365 - 113365

Published: Oct. 23, 2024

Language: Английский

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mTOR/EGFR/iNOS/MAP2K1/FGFR/TGFB1 Are Druggable Candidates for N-(2,4-Difluorophenyl)-2′,4′-Difluoro-4-Hydroxybiphenyl-3-Carboxamide (NSC765598), With Consequent Anticancer Implications

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: March 26, 2021

The application of computational and multi-omics approaches has aided our understanding carcinogenesis the development therapeutic strategies. NSC765598 is a novel small molecule derivative salicylanilide. This study aims to investigate ligand-protein interactions with its potential targets evaluate anticancer activities in vitro.We used multi-computational tools clinical databases, respectively, identify drug target for analyze genetic profile prognostic relevance multiple cancers. We evaluated vitro against National Cancer Institute 60 (NCI60) human tumor cell lines molecular docking interactions. Finally, we DTP-COMPARE algorithm compare fingerprints NCI standard agents.We identified mammalian rapamycin (mTOR)/epidermal growth factor receptor (EGFR)/inducible nitric oxide synthase (iNOS)/mitogen-activated protein 2 kinase 1 (MAP2K1)/fibroblast (FGFR)/transforming factor-β1 (TGFB1) as NSC765598. were enriched cancer-associated pathways, overexpressed Among targets, alterations occurred most frequently EGFR (7%), particularly glioblastoma, esophageal squamous cancer, head neck non-small-cell lung associated poor prognoses survival patients, while other less altered. displayed selective antiproliferative cytotoxic preferences NSCLC (50% inhibition (GI50) = 1.12-3.95 µM; total (TGI) 3.72-16.60 μM), leukemia (GI50 1.20-3.10 TGI 3.90-12.70 melanoma 1.45-3.59 µM), renal cancer 1.38-3.40 4.84-13.70 μM) lines, panels colon, breast, ovarian, prostate, central nervous system (CNS) sensitive Interestingly, docked well into binding cavity by conventional H-bonds, van der Waal forces, variety π-interactions, higher (ΔG -11.0 kcal/mol), NOS2 mTOR -8.8 kcal/mol). shares similar anti-cancer agents acceptable physicochemical values met criteria drug-likeness.NSC765598 significant multi-target properties, thus serve candidate worthy further preclinical studies.

Language: Английский

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Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade

Life Science Alliance, Journal Year: 2022, Volume and Issue: 5(6), P. e202101230 - e202101230

Published: March 2, 2022

Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape TME toward immunosuppressive milieu and attenuate efficacy immune checkpoint blockade (ICB) therapy. However, detailed mechanism how heterogeneous regulate response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by expression Meflin, glycosylphosphatidylinositol-anchored protein marker mesenchymal stromal/stem cells, is associated with survival favorable therapeutic monotherapy in patients non-small cell lung cancer (NSCLC). The prevalence Meflin-positive was positively correlated CD4-positive T-cell infiltration vascularization within tumors. Meflin deficiency CAF-specific overexpression resulted defective enhanced responses syngeneic tumors mice, respectively. These findings suggest presence promotes efficacy, which adds our understanding functions heterogeneity.

Language: Английский

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The regulatory role of PDE4B in the progression of inflammatory function study

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

Inflammation is a response of the body to external stimuli (eg. chemical irritants, bacteria, viruses, etc.), and when are persistent, they tend trigger chronic inflammation. The presence inflammation an important component tumor microenvironment produced by variety inflammatory cells macrophages, neutrophils, leukocytes, etc.). relationship between cancer development has been widely accepted, associated with many cancers, including bronchitis lung cancer, cystitis inducing bladder cancer. Moreover, colorectitis more likely develop into colorectal Therefore, specific cellular mechanisms hot topic research. Recent studies have identified phosphodiesterase 4B (PDE4B), member (PDEs) protein family, as major cyclic AMP (cAMP) metabolizing enzyme in cells, therapeutic role PDE4B inflammation, In this review, we will present tumors potential clinical application.

Language: Английский

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Mucinous adenocarcinoma: A unique clinicopathological subtype in colorectal cancer

World Journal of Gastrointestinal Surgery, Journal Year: 2021, Volume and Issue: 13(12), P. 1567 - 1583

Published: Dec. 23, 2021

Mucinous adenocarcinoma (MAC) is a unique clinicopathological subtype of colorectal cancer, which characterized by extracellular mucinous components that comprise at least 50% the tumor tissue. The clinical characteristics, molecular features, response to chemo-/radiotherapy, and prognosis MAC are different from non-MAC (NMAC). more common in proximal colon, with larger volume, higher T-stage, proportion positive lymph nodes, poorer differentiation, peritoneal implants compared NMAC. Although biopsy main diagnostic method for MAC, magnetic resonance imaging superior accuracy, especially rectal carcinoma. aberrant expression mucins, including MUC1, MUC2 MUC5AC, notable feature may be related invasion, metastasis, inhibition apoptosis, chemo-/radiotherapy resistance. genetic origin mainly BRAF mutation, microsatellite instability, CpG island methylator phenotype pathway. In addition, poor has been confirmed various studies, colonic still controversial. this review, we summarize epidemiology, methods diagnosis, treatments order provide references further fundamental research.

Language: Английский

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