Editorial: Utilizing omics strategies to discover new drug targets for cancers DOI Creative Commons
Shujun Zhang, Chen Xue, Xinyu Gu

et al.

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

Published: Nov. 27, 2024

Utility of Omics Strategies to Discover New Drug Targets for Cancers Cancer is a major public health issue and significant contributor the global disease burden. Since 2010, different kinds cancer have become main cause deaths in China, with incidence, mortality burden all escalating. Data shows that approximately 10 million people die from globally each year, China accounting around 30% this figure (Qi et al., 2023). The incidence rates increase exponentially age, given aging world population, it expected number cancer-related both on scale will continue rise, causing huge costs. Currently, treatment methods include surgery, radiotherapy, chemotherapy, targeted therapy. Surgery usually first-line approach most tumors, suitable patients early stage. Radiotherapy chemotherapy are generally used as complementary options after surgery or who no possibility surgery. Targeted therapy addresses gene mutations has better efficacy, while individual differences emergence drug resistance necessitate discovering new targets development more therapeutic drugs.The pathogenesis involves complex reorganizations various genetic, transcriptional, proteomic, metabolomic processes drive tumor development.Several omics technologies been shown exhibit great potential research, which genomics, epigenetics, transcriptomics, proteomics, metabolomics. Genomics one essential field.Genome sequencing enables researchers identify progression. Meanwhile, epigenetics analysis comprehensive description epigenetic profile patients, referring occurrence, growth, metastasis, immune evasion tumors. Transcriptomics can capture changes between expression patterns cells normal cells, providing perspective molecular occur cancer. Proteomics quantify proteins present tissues insights into functional cancer.Metabolomics detect alterations metabolic cancer, thereby deeper understanding dependences growth.More specifically, genomics examines DNA sequences deciphers genetic information encoded genome. By comparing genomes those healthy scientists pinpoint specific growth. These findings provide clues identifying be develop precise therapies. Epigenetic affect function through chemical modifications nucleotides proteins. There growing evidence play an important role occurrence human cancers; many biomarkers also found Another strategy studying genes cells.By over-or underexpressed prioritize these candidates research. facilitates discovery targets, dysregulated support Restoring protein inhibiting abnormal activity correct cell states mitigate Metabolomics study small molecules pathways, playing Identifying pathways critical survival opens up avenues drugs selectively target pathways.SCLC aggressive neuroendocrine (NE) strong proliferation metastasis potential, resistance, poor prognosis (Megyesfalvi Although immunotherapy greatly improved non-SCLC (NSCLC), advancement SCLC treatments slow, improvement achieved rate therefore still outside field precision medicine. integrating mRNA, phosphorylation data 107 unsupervised clustering based non-negative matrix decomposition (NMF) was applied divide four subtypes: nmf1, nmf2, nmf3, nmf4 (Liu 2024). Firstly, multi-omics revealed nmf1 subtypes were mainly enriched cycle, damage, chromatin organization, regulatory had response score ATR TOP1 inhibition. level NOTCH ligand delta-like 3(DLL3) highest nmf2 subtype. Therefore, subtype likely benefit therapies targeting DLL3. Secondly, phosphorylated proteomic showed RTK signaling significantly upregulated nmf3 Thus, may treat characterized by high MYC enrichment RNA preferentially associated AURKA amplification, further suggesting opportunities AURKA. Multiomics expand our events malignancies contribute effective clinical type.In triple negative breast (TNBC), genomic transcriptomic strategies indicated programmed death ligand-1 (PD-L1) mutational overexpressed about 20% TNBC thus serve (Kudelova 2022). Upon study, anti-PD-L1 antibody atezolizumab became first FDA-approved locally advanced metastatic TNBC. In addition, application facilitated deriving other cancers, such (Neagu 2023), lung (Yan 2024), gastric (Hou, Zhao Zhu hematological (Rosenquist etc. integration approaches accelerated

Language: Английский

Targeted therapy and immunotherapy for gastric cancer: rational strategies, novel advancements, challenges, and future perspectives DOI Creative Commons
Dong Luo, Yunmei Liu, Zhengmao Lu

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Feb. 8, 2025

Abstract Gastric cancer (GC) is one of the most common malignant tumors worldwide, and its treatment has been a focus medical research. Herein we systematically review current status advancements in targeted therapy immunotherapy for GC, which have emerged as important strategies recent years with great potential, summarize efficacy safety such treatments. Targeted therapies against key targets including epidermal growth factor receptor (EGFR), human 2 (HER2), vascular endothelial (VEGF)/VEGF (VEGFR), shown remarkable therapeutic efficacies by inhibiting tumor progression and/or blood supply. In particular, markable breakthroughs made HER2-targeting drugs HER2-positive GC patients. To address intrinsic acquired resistances to drugs, novel agents bispecific antibodies antibody–drug conjugates (ADC) targeting HER2 developed. Immunotherapy enhances recognition elimination cells activating body anticancer immune system. Programmed cell death protein 1 (PD-1) programmed death-ligand (PD-L1) are commonly used immunotherapeutic some success treatment. Innovative modalities, adoptive therapy, vaccines, non-specific immunomodulators oncolytic viruses promise early-stage clinical trials GC. Clinical supported that can significantly improve survival quality life However, effects need be further improved more personalized, advancement researches on microenvironment. Further studies remain needed issues drug resistance adverse events pertaining The combined application individualized should explored developed, provide effective treatments

Language: Английский

Citations

2
Exploring Immune Checkpoint Inhibitors: Focus on PD-1/PD-L1 Axis and Beyond DOI
Durre Aden, Samreen Zaheer, Niti Sureka

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 269, P. 155864 - 155864

Published: March 1, 2025

Language: Английский

Citations

2
Immunotherapy and Cancer: The Multi-Omics Perspective DOI Open Access

Clelia Donisi,

Andrea Pretta, Valeria Pusceddu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3563 - 3563

Published: March 21, 2024

Immunotherapies have revolutionized cancer treatment approaches. Because not all patients respond positively to immune therapeutic agents, it represents a challenge for scientists who strive understand the mechanisms behind such resistance. In-depth exploration of tumor biology, using novel technologies as omics science, can help decode role microenvironment (TIME) in producing response blockade strategies. It also identify biomarkers patient stratification and personalized treatment. This review aims explore these new models highlight their possible pivotal changing clinical practice.

Language: Английский

Citations

10
Identification of CKAP2 as a Potential Target for Prevention of Gastric Cancer Progression: A Multi-Omics Study DOI Open Access
Xueyi Liu, Wenyu Zhang, Hui Wang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1557 - 1557

Published: Feb. 12, 2025

Gastric cancer (GC) ranks as one of the most prevalent malignant tumors globally. The subtle manifestation its early-stage symptoms often results in many GC patients being diagnosed at a late or advanced stage, thereby posing significant obstacles to effectiveness chemotherapy treatments. Therefore, identifying early biomarkers for is crucial. In recent years, an increasing number studies have highlighted pivotal role that aging plays progression cancer. Among various proteins involved, Cytoskeleton-associated protein 2 (CKAP2) emerges crucial player controlling cell proliferation, regulating mitosis and division, exerting influence on process. We employed bioinformatics approach assess causal association between aging-related genes explore potential significance CKAP2 by analyzing data sourced from repositories, including Genotype Tissue Expression (GTEx), GWAS Catalog, Database Cell Senescence Genes (CellAge), Cancer Genome Atlas (TCGA), Gene Omnibus (GEO), Human Protein (HPA), Comparative Toxicology (CTD). Our research summarized relationship expression development risk GC, differential with prognosis genetic correlation, functional analysis, immune infiltration, explored interaction chemical substances. findings revealed elevation correlated reduced likelihood developing GC. There was difference normal patients. Specifically, there higher compared addition, has been proven diagnostic value elevated levels are indicative more favorable prognosis. Immune infiltration analysis tumor microenvironment, while (CTD) identified small molecule compound may target CKAP2. summary, through comprehensive multivariate analyses, we validated play shows indicator both diagnosis making it worthy further clinical investigation.

Language: Английский

Citations

1
Reprogramming tumor-associated macrophages in gastric cancer: a pathway to enhanced immunotherapy DOI Creative Commons
Yibo He, Qianran Hong, Shiliang Chen

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Gastric cancer (GC) remains a significant global health concern due to its poor prognosis and limited therapeutic options, particularly in advanced stages. Tumor microenvironment (TME), tumor-associated macrophages (TAMs), plays key role tumor progression, immune evasion, therapy resistance. TAMs exhibit plasticity, shifting between pro-inflammatory M1 immunosuppressive M2 phenotypes, with the latter predominating GC contributing outcomes. Recent advancements focus on targeting TAMs, including inhibiting polarization, reprogramming combining TAM-targeted approaches checkpoint inhibitors. Innovations nanotechnology, metabolic reprogramming, pathways such as interleukin-6 C-C motif ligand 2/C-C chemokine receptor 2 further enhance these strategies. However, challenges remain, spatial functional heterogeneity of within TME need for selective avoid disrupting homeostasis. Ongoing research TAM origins, functions, interactions is crucial developing precise effective therapies. These advances hold promise not only improving outcomes but also addressing other cancers similarly complex microenvironments.

Language: Английский

Citations

1
Nanomaterials in gastric cancer: pioneering precision medicine for diagnosis, therapy, and prevention DOI

Tiantian Liu,

Ying-Qiu Gu, Zaili Yang

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(4)

Published: March 6, 2025

Language: Английский

Citations

1
Role of MARK2 in the nervous system and cancer DOI
Yining Lei, Ruyi Zhang, Fei Cai

et al.

Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: 31(4), P. 497 - 506

Published: Feb. 2, 2024

Language: Английский

Citations

4
Jumonji domain-containing protein 6 promotes gastric cancer progression: Modulating immune evasion through autophagy and oxidative stress pathways DOI Open Access
Xinyue Zhang, Na Di

CytoJournal, Journal Year: 2025, Volume and Issue: 22, P. 6 - 6

Published: Jan. 23, 2025

Objective: Immune response is crucial in the development of gastric cancer (GC), and Jumonji domain-containing protein 6 (JMJD6) plays an important role mediating GC cell behavior. This study aims to elucidate mechanisms through which JMJD6 affects autophagy immune evasion cells. Material Methods: Immunocytochemistry was employed assess programmed death-ligand 1 (PD-L1) levels line (MKN-45) epithelial MKN-45 cells with knockdown overexpression were generated. The effect on evaluated using counting kit-8 assay, cellular fluorescence staining, Transwell assays. Western blot analysis immunofluorescence techniques investigate regulation by JMJD6. Reactive oxygen species (ROS) applying ROS staining. Meanwhile, gene expression molecules related antioxidant stress responses assessed assays quantitative real-time polymerase chain reactions, respectively. Results: PD-L1 elevated ( P < 0.001). enhanced migration, invasion, colony formation vitro In cells, epithelial-mesenchymal transition promoted upregulation but notably inhibited increased Sequestosome 1, Microtubule-associated 1A/1B-light 3 (LC3)II/LC3I, activation further addition, reduced production response, reverse effects observed Conclusion: facilitates progression modulating oxidative pathways.

Language: Английский

Citations

0
The role and application of bioinformatics techniques and tools in drug discovery DOI Creative Commons
Shujun Zhang, Kaijie Liu, Yafeng Liu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 13, 2025

The process of drug discovery and development is both lengthy intricate, demanding a substantial investment time financial resources. Bioinformatics techniques tools can not only accelerate the identification targets screening refinement candidates, but also facilitate characterization side effects prediction resistance. High-throughput data from genomics, transcriptomics, proteomics, metabolomics make significant contributions to mechanics-based reuse. This paper summarizes bioinformatics technologies in research their roles applications development, aiming provide references for new drugs realization precision medicine.

Language: Английский

Citations

0
A Novel Prognostic Marker Based on Metabolic Gene for Gastric Cancer Patients Receiving Immunotherapy DOI
Hao Xu,

Xiaohuan Yuan,

Xin Song

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0