Recent Advances in the Clinical Translation of Small-Cell Lung Cancer Therapeutics

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 255 - 255

Published: Jan. 14, 2025

Small-cell lung cancer (SCLC) is a recalcitrant form of cancer, representing 15% cases globally. SCLC classified within the range neuroendocrine pulmonary neoplasms, exhibiting shared morphologic, ultrastructural, immunohistochemical, and molecular genomic features. It marked by rapid proliferation, propensity for early metastasis, an overall poor prognosis. The current conventional therapies involve platinum–etoposide-based chemotherapy in combination with immunotherapy. Nonetheless, emergence therapeutic resistance continues to pose substantial difficulties. profiling uncovers significant chromosomal rearrangements along considerable mutation burden, typically involving functional inactivation tumor suppressor genes TP53 RB1. Identifying biomarkers evaluating new treatments crucial enhancing outcomes patients SCLC. Targeted such as topoisomerase inhibitors, DLL3 HDAC PARP Chk1 etc., have introduced options future applications. In this review, we will attempt outline key pathways that play role development progression SCLC, together comprehensive overview most recent advancements novel targeted treatment strategies, well some ongoing clinical trials against goal improving patient outcomes.

Language: Английский

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High LGALS3 expression induced by HCP5/hsa-miR-27b-3p correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 20, 2024

Hepatocellular carcinoma (HCC) is widely recognized for its unfavorable prognosis. Increasing evidence has revealed that LGALS3 an essential function in initiating and developing several malignancies humans. Nevertheless, thorough analysis of the expression profile, clinical prognosis, pathway prediction, immune infiltration not been fully explored HCC.

Language: Английский

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NEK2 contributes to radioresistance in esophageal squamous cell carcinoma by inducing protective autophagy via regulating TRIM21

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 23, 2024

Abstract Background Radiotherapy (RT) has been identified as a vital treatment for esophageal squamous cell carcinoma (ESCC), while the development of radioresistance remains major obstacle in ESCC management. The aim this study was to investigate effect NIMA-related kinase 2 (NEK2) on cells and reveal potential molecular mechanisms. Methods Human epithelial (HEEC) human lines were obtained from Research Center Fourth Hospital Hebei Medical University (Shijiazhuang, China). Cell Counting Kit-8 (CCK-8) flow cytometry assays applied assess proliferation ability, cycle, apoptosis rates, ROS production cells. colony-forming assay used estimate NEK2 radiosensitivity. Autophagy investigated by western blotting analysis, GFP-mRFP-LC3 fluorescence assay, transmission electron microscopy (TEM). Results In present study, our results showed that associated with radioresistance, cycle arrest, apoptosis, production, survival ESCC. knockdown could significantly inhibit growth enhancing radiosensitivity Interestingly, inhibited autophagy reduced autophagic flux, ultimately reversing NEK2-induced radioresistance. Mechanistically, bound regulated stability tripartite motif-containing protein 21 (TRIM21). accumulation light chain 3 beta (LC3B II) can be reversed TRIM21. Conclusion These demonstrated activated through TRIM21, which may provide promising therapeutic strategy elucidating NEK2-mediated

Language: Английский

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Transient activation of YAP/TAZ confers resistance to morusin-induced apoptosis

BMC Molecular and Cell Biology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 20, 2025

The Hippo signaling pathway involves a kinase cascade that controls phosphorylation of the effector proteins YAP and TAZ, leading to regulation cell growth, tissue homeostasis, apoptosis. Morusin, compound extracted from Morus alba, has shown potential in cancer therapy by targeting multiple pathways, including PI3K/Akt/mTOR, JAK/STAT, MAPK/ERK, apoptosis pathways. This study explores effects morusin on activation its implications for resistance. Our investigation revealed induces transient activation, characterized dephosphorylation at S127 nuclear localization, followed gradual rephosphorylation cells. Notably, this occurs independently canonical LATS1/2, MINK1, MAPK pathways during inactivation stage. Furthermore, morusin-induced stress granule formation was significantly impaired YAP/TAZ-depleted cells, suggesting role Additionally, expression constitutively active MINK1 maintained reduced apoptosis, indicating prolonged can enhance resistance death. These findings suggest YAP/TAZ are crucial could anti-cancer efficacy morusin. provides new insights into molecular mechanisms morusin, highlighting therapeutic strategies against disrupting

Language: Английский

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Overexpression of metalloproteinase PAPPA accelerates cancer progression and correlates with immune cell infiltration in gastric cancer: insights from bioinformatics and in vitro investigations

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 7, 2025

Gastric cancer (GC) is one of the most common malignant tumors in digestive system. However, development its targeted therapies has been slow. Therefore, exploring mechanisms behavior GC key to developing their treatment methods. Pregnancy-associated plasma protein-A(PAPPA) thought play an important role occurrence and progression cancer, yet significance not reported. Bioinformatics analysis elucidated PAPPA's expression prognostic significance. The study correlated PAPPA with immune infiltration signaling pathways. Cellular assays, including CCK-8, Western blotting, flow cytometry, were utilized examine gastric cell apoptosis, migration, invasion. demonstrated that upregulated correlates poor prognosis. Correlation Cox regression analyses have revealed TNM staging, pathological age, outcome assessment, postoperative tumor residue, are determinants GC. Further indicates associated various cells pathways related experiments shown promotes proliferation, deficiency can inhibit proliferation cells, inducing cycle arrest at G1/S phase. findings this investigation suggest serves as a crucial modulator GC, underscoring potential target.

Language: Английский

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Immunotherapies Targeting CD123 and CD303: A New Frontier in Treating Blastic Plasmacytoid Dendritic Cell Neoplasm

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2732 - 2732

Published: March 18, 2025

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy characterized by the overexpression of CD123 CD303 surface antigens. These molecular markers play crucial role in diagnosing diseases developing targeted therapies. Traditional treatment options for BPDCN have demonstrated limited effectiveness, highlighting need new innovative therapeutic strategies. Recent advances immunotherapy, particularly monoclonal antibodies, bispecific T-cell engagers, CAR therapy, provided promising alternatives. Tagraxofusp, first FDA-approved CD123-targeted has significantly improved patient outcomes. Additionally, emerging CD303-targeting strategies offer potential further advancements. Despite these breakthroughs, challenges such as resistance toxicity remain. This review explores latest developments treatment, emphasizing targets precision medicine interventions. The ongoing evolution immunotherapies holds promise improving survival redefining paradigms malignancies.

Language: Английский

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Functional Characterization of miR-216a-5p and miR-125a-5p on Pancreatic Cancer Stem Cells

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2830 - 2830

Published: March 21, 2025

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death. Its poor prognosis closely related to late-stage diagnosis, which results from both nonspecific symptoms and absence biomarkers for early diagnosis. MicroRNAs (miRNAs) exert a regulatory role in numerous biological processes their aberrant expression has been found broad spectrum diseases, including cancer. Cancer stem cells (CSCs) represent driving force PDAC initiation, progression, metastatic spread. Our previous research highlighted interesting behavior miR-216a-5p miR-125a-5p progression CSC phenotype. The present study aimed evaluate effect on acquisition or suppression pancreatic traits. BxPC-3, AsPC-1 cell lines, CSC-like models were transfected with mimics inhibitors. Following transfection, we evaluated impact surface markers (CD44/CD24/CxCR4), ALDH1 activity, pluripotency- EMT-related gene expression, clonogenic potential. show that enhances CD44/CD24/CxCR4 while negatively affecting activity EMT genes. MiR-216a-5p positively influenced property. MiR-125a-5p promoted inhibiting activity. It enhanced Snail, Oct-4, Sox-2, potential appeared be affected. Comprehensively, our provide further knowledge miRNAs CSCs. Moreover, they corroborate findings about miR-216a-5p’s dual miR-125a-5p’s promotive function PDAC.

Language: Английский

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The role of ncRNAs and exosomes in the development and progression of endometrial cancer

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

Published: Aug. 12, 2024

Endometrial cancer (EC) is one of the most common gynecologic cancers. In recent years, research has focused on genetic characteristics tumors to detail their prognosis and tailor therapy. case EC, mutations have been shown underlie formation. It very important know mechanisms EC formation related induced by estrogen, among other things. Noncoding RNAs (ncRNAs), composed nucleotide transcripts with low protein-coding capacity, are proving be important. Their expression patterns in many malignancies can inhibit tumor progression. They also regulate protein coding at epigenetic, transcriptional, posttranscriptional levels. MicroRNAs (miRNAs), several varieties which associated normal endometrium as well its tumor, play a particularly role gene expression. MiRNAs long noncoding (lncRNAs) affect pathways tissues roles development, invasion, metastasis, resistance anticancer drugs through such suppression apoptosis progression stem cells. worth noting that miRNAs highly precise, sensitive, robust, making them potential markers for diagnosing cancers Unfortunately, incidence increases, treatment becomes challenging limited invasive tools. The prospect using microRNAs candidates diagnostic therapeutic use seems promising. Exosomes extracellular vesicles released from types cells, including contain proteins, DNA, various RNA, miRNAs. RNA components exosomes vary widely, depending physiology tissue cells they originate. both DNA communication functions between Exosomal mediate tumor-associated fibroblasts (CAFs), macrophages (TAMs) key cell proliferation microenvironment Oncogenes carried induce malignant transformation target During synthesis exosomes, factors, proteomic data upregulated. Thus, considered an interesting diagnosis endometrial analyzing biomarkers contained exosomes. Expression miRNAs, miR-15a-5p, was elevated derived plasma patients. This may suggest utility this biomarker EC. researchers become interested topic prognostic there still too few identified support cancer. Further into effects ncRNAs allow breakthroughs.

Language: Английский

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Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 17, 2024

Abstract Background Drug resistance poses a significant challenge in cancer treatment, particularly as leading cause of therapy failure. Cisplatin, the primary drug for lung adenocarcinoma (LUAD) chemotherapy, shows effective treatment outcomes. However, development against cisplatin is major obstacle. Therefore, identifying genes resistant to and adopting personalized could significantly improve patient Methods By examining transcriptome data cisplatin-resistant LUAD cells from GEO database, 181 associated with were identified. Using univariate regression analysis, random forest multivariate analyses, two prognostic genes, E2F7 FAM83A, This study developed model utilizing FAM83A key indicators. The Cell Counting Kit 8 assay, Transwell flow cytometry used detect effects on proliferation, migration, invasiveness apoptosis A549/PC9 cells. Western blotting was determine effect AKT/mTOR signaling pathway. Results has pinpointed crucial resistance, comprehensive assist diagnosis, prognosis, evaluation relapse risk LUAD. Analysis revealed that patients at higher risk, according these genetic markers, had elevated levels immune checkpoints (PD-L1 PD-L2). diagnosis values further confirmed clinical data. Furthermore, inhibiting markedly reduced their invasion, increased apoptosis. In vivo experiments corroborated findings, showing tumor growth metastasis upon suppression models. Conclusion Our affirms value based DEGs, offering reliable method predicting success immunotherapy diagnostic predictive demonstrates excellent performance. vitro, reducing antitumor by blocking progression. Further investigation into molecular mechanisms highlighted E2F7’s pathway, underscoring its therapeutic potential. era medicine, this DEG-based promises guide practice.

Language: Английский

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Single-cell RNA sequencing identifies the expression of hemoglobin in chondrocyte cell subpopulations in osteoarthritis

BMC Molecular and Cell Biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Dec. 30, 2024

In recent years, chondrocytes have been found to contain hemoglobin, which might be an alternative strategy for adapting the hypoxic environment, while potential mechanisms of that is still unclear. Here, we report expression characteristics and associated pathways hemoglobin in using single-cell RNA sequencing (scRNA-seq). We downloaded data normal people patients with osteoarthritis (OA) from Gene Expression Omnibus (GEO) database cells are unbiased clustered based on gene pattern. determined levels various chondrocyte subpopulations. Meanwhile, further explored difference enriched signaling cell-cell interaction high-expression low-expression groups. Specifically, SPP1 was closely OA progression. Our findings provide new insights into distribution clues underlying role related that, providing ideas treatment OA.

Language: Английский

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