Machine Learning-Based Approach to Developing Potent EGFR Inhibitors for Breast Cancer─Design, Synthesis, and In Vitro Evaluation DOI Creative Commons
Hossam Nada, Anam Rana Gul, Ahmed Elkamhawy

и другие.

ACS Omega, Год журнала: 2023, Номер 8(35), С. 31784 - 31800

Опубликована: Авг. 23, 2023

The epidermal growth factor receptor (EGFR) is vital for regulating cellular functions, including cell division, migration, survival, apoptosis, angiogenesis, and cancer. EGFR overexpression an ideal target anticancer drug development as it absent from normal tissues, marking tumor-specific. Unfortunately, the of medication resistance limits therapeutic efficacy currently approved inhibitors, indicating need further development. Herein, a machine learning-based application that predicts bioactivity novel inhibitors presented. Clustering small-molecule inhibitor (∼9000 compounds) library showed N-substituted quinazolin-4-amine-based compounds made up largest cluster (∼2500 compounds). Taking advantage this finding, rational design was used to series 4-anilinoquinazoline-based which were first tested by developed artificial intelligence application, only predicted be active then chosen synthesized. This led synthesis 18 compounds, subsequently evaluated cytotoxicity inhibitory activity. Among compound 9 demonstrated most potent antiproliferative activity, with 2.50 1.96 μM activity over MCF-7 MDA-MB-231 cancer lines, respectively. Moreover, displayed 2.53 nM promising apoptotic results, potential candidate breast therapy.

Язык: Английский

Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy DOI Creative Commons
Xiaoting Luo, Xin He, Xingmei Zhang

и другие.

MedComm, Год журнала: 2024, Номер 5(2)

Опубликована: Фев. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a high mortality rate. It regarded as significant public health issue because of its complicated pathophysiology, metastasis, and recurrence rates. There are no obvious symptoms in early stage HCC, which often leads to delays diagnosis. Traditional treatment methods such surgical resection, radiotherapy, chemotherapy, interventional therapies have limited therapeutic effects for HCC patients or metastasis. With development molecular biology immunology, signaling pathways immune checkpoint were identified main mechanism progression. Targeting these molecules has become new direction HCC. At present, combination targeted drugs inhibitors first choice advanced patients. In this review, we mainly focus on cutting‐edge research corresponding therapy immunotherapy great significance comprehensively understand pathogenesis search potential targets, optimize strategies

Язык: Английский

Процитировано

32
Using a pan-cancer atlas to investigate tumour associated macrophages as regulators of immunotherapy response DOI Creative Commons
Alexander Coulton, Jun Murai, Danwen Qian

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 6, 2024

Abstract The paradigm for macrophage characterization has evolved from the simple M1/M2 dichotomy to a more complex model that encompasses broad spectrum of phenotypic diversity, due differences in ontogeny and/or local stimuli. We currently lack an in-depth pan-cancer single cell RNA-seq (scRNAseq) atlas tumour-associated macrophages (TAMs) fully captures this complexity. In addition, increased understanding diversity could help explain variable responses cancer patients immunotherapy. Our includes well established subsets as number additional ones. associate composition with tumour phenotype and show can vary between primary metastatic tumours growing sites like liver. also examine macrophage-T functional cross talk identify two TAMs associated T activation. Analysis TAM signatures large cohort immune checkpoint inhibitor-treated (CPI1000 + ) multiple response, including presence subset upregulate collagen-related genes. Finally, we demonstrate utility our data resource reference mapping novel datasets using projection. Overall, these advances represent important step both classification overcoming resistance immunotherapies cancer.

Язык: Английский

Процитировано

26
Targeting the EGFR signalling pathway in metastatic colorectal cancer DOI
Stefania Napolitano, Giulia Martini, Davide Ciardiello

и другие.

˜The œLancet. Gastroenterology & hepatology, Год журнала: 2024, Номер 9(7), С. 664 - 676

Опубликована: Апрель 30, 2024

Язык: Английский

Процитировано

16
Emerging roles of cystathionine β-synthase in various forms of cancer DOI Creative Commons
Kelly Ascenção, Csaba Szabó

Redox Biology, Год журнала: 2022, Номер 53, С. 102331 - 102331

Опубликована: Май 10, 2022

The expression of the reverse transsulfuration enzyme cystathionine-β-synthase (CBS) is markedly increased in many forms cancer, including colorectal, ovarian, lung, breast and kidney, while other cancers (liver cancer glioma) it becomes downregulated. According to clinical database data high-CBS-expressor (e.g. colon or ovarian cancer), high CBS typically predicts lower survival, low-CBS-expressor liver low associated with survival. In high-CBS expressing tumor cells, CBS, its product hydrogen sulfide (H2S) serves as a bioenergetic, proliferative, cytoprotective stemness factor; also supports angiogenesis epithelial-to-mesenchymal transition microenvironment. current article reviews various tumor-cell-supporting roles CBS/H2S axis expressor overviews anticancer effects silencing pharmacological inhibition models vitro vivo; outlines potential approaches for biomarker identification, support future targeted therapies based on inhibition.

Язык: Английский

Процитировано

67
Single-cell transcriptomics and epigenomics unravel the role of monocytes in neuroblastoma bone marrow metastasis DOI Creative Commons
Irfete S. Fetahu, Wolfgang Esser‐Skala, Rohit Dnyansagar

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 26, 2023

Metastasis is the major cause of cancer-related deaths. Neuroblastoma (NB), a childhood tumor has been molecularly defined at primary cancer site, however, bone marrow (BM) as metastatic niche NB poorly characterized. Here we perform single-cell transcriptomic and epigenomic profiling BM aspirates from 11 subjects spanning three subtypes compare these to five age-matched metastasis-free BM, followed by in-depth single cell analyses tissue diversity cell-cell interactions, well functional validation. We show that cellular plasticity cells conserved upon metastasis type composition subtype-dependent. signal microenvironment, rewiring via macrophage mgration inhibitory factor midkine signaling specifically monocytes, which exhibit M1 M2 features, are marked activation pro- anti-inflammatory programs, express tumor-promoting factors, reminiscent tumor-associated macrophages. The interactions pathways characterized in our study provide basis for therapeutic approaches target tumor-to-microenvironment interactions.

Язык: Английский

Процитировано

34
The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy DOI Creative Commons
Bo Hou, Ting Chen, He Zhang

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Янв. 17, 2023

The tumor microenvironment (TME) is the surrounding environment, which critical for development and progression. TME also involved in clinical intervention treatment outcomes. Modulation of useful improving therapy strategies. PD-L1 protein on cells interacts with PD-1 T cells, contributing to cell dysfunction exhaustion, blockage immune response. Evidence has demonstrated that expression PD-1/PD-L1 associated response anti-PD-1/PD-L1 cancer patients. It important discuss regulatory machinery how finely regulated cells. In recent years, studies have was governed by various E3 ubiquitin ligases TME, resistance human cancers. this review, we will role molecular mechanisms ligases-mediated regulation TME. Moreover, describe ligases-involved alters efficacy. Altogether, targeting control levels could be a potential strategy potentiate immunotherapeutic effects

Язык: Английский

Процитировано

26
Single-Cell Chromatin Accessibility Analysis Reveals the Epigenetic Basis and Signature Transcription Factors for the Molecular Subtypes of Colorectal Cancers DOI
Zhenyu Liu,

Yuqiong Hu,

Haoling Xie

и другие.

Cancer Discovery, Год журнала: 2024, Номер 14(6), С. 1082 - 1105

Опубликована: Март 5, 2024

Abstract Colorectal cancer is a highly heterogeneous disease, with well-characterized subtypes based on genome, DNA methylome, and transcriptome signatures. To chart the epigenetic landscape of colorectal cancers, we generated high-quality single-cell chromatin accessibility atlas epithelial cells for 29 patients. Abnormal states acquired in adenomas were largely retained which tightly accompanied by opposite changes methylation. Unsupervised analysis malignant revealed two subtypes, exactly matching iCMS classification, key iCMS-specific transcription factors (TFs) identified, including HNF4A PPARA iCMS2 tumors FOXA3 MAFK iCMS3 tumors. Notably, subtype-specific TFs bind to distinct target gene sets contribute both interpatient similarities diversities accessibilities RNA expressions. Moreover, identified CpG-island methylator phenotypes pinpointed state signatures TF regulators CIMP-high subtype. Our work systematically basis well-known CIMP classifications cancers. Significance: minor major genes can faithfully explain corresponding expression respectively. This article featured Selected Articles from Issue, p. 897

Язык: Английский

Процитировано

11
Molecular docking, QSAR, and simulation analyses of EGFR-targeting phytochemicals in non-small cell lung cancer DOI
Md. Enamul Kabir Talukder,

Md. Farhan Atif,

Noimul Hasan Siddiquee

и другие.

Journal of Molecular Structure, Год журнала: 2024, Номер 1321, С. 139924 - 139924

Опубликована: Сен. 3, 2024

Язык: Английский

Процитировано

9
Novel T cell exhaustion gene signature to predict prognosis and immunotherapy response in thyroid carcinoma from integrated RNA-sequencing analysis DOI Creative Commons
Yang Li, Zhen Wang,

Fangting Lu

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 10, 2024

Abstract Exhausted CD8 + T lymphocytes and tumor-associated macrophages play critical roles in determining cancer prognosis the efficacy of immunotherapy. Our study revealed a negative correlation between exhausted thyroid carcinoma (THCA). Consensus clustering divided patients into two subgroups exhaustion with different prognoses, as defined by marker genes cells. Subsequently, we constructed an eight-gene prognostic signature, developed risk score named exhaustion-related gene (ERGS) to forecast both immunotherapy response THCA. Bulk RNA sequencing analysis higher prevalence M2 macrophages, indicative immunosuppressive tumor microenvironment (TME), high-ERGS group. Single-cell showed that SPP1 CD14 monocytes infiltrations were positively associated ERGS. Functionally, it was determined exert role, while implicated promoting progression angiogenesis. Analysis cell–cell interactions cells highlighted activation SPP1-CD44 MIF-CD74 axes, which could foster TME. Therapeutic strategies target monocytes, axes may potentially improve amplify THCA patients.

Язык: Английский

Процитировано

8
Spotlight on ideal target antigens and resistance in antibody-drug conjugates: Strategies for competitive advancement DOI
Mingxia Jiang, Qiao Li, Binghe Xu

и другие.

Drug Resistance Updates, Год журнала: 2024, Номер 75, С. 101086 - 101086

Опубликована: Апрель 23, 2024

Язык: Английский

Процитировано

8