Small cell lung cancer profiling: an updated synthesis of subtypes, vulnerabilities, and plasticity

Trends in cancer, Год журнала: 2024, Номер 10(10), С. 935 - 946

Опубликована: Авг. 19, 2024

Язык: Английский

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Single‐Cell RNA Sequencing Reveals the Cellular Origin and Evolution of Small‐Cell Neuroendocrine Carcinoma of the Cervix

Journal of Medical Virology, Год журнала: 2025, Номер 97(1)

Опубликована: Янв. 1, 2025

Small-cell neuroendocrine cancer (SCNEC) of the uterine cervix is an exceedingly rare, highly aggressive tumor with extremely poor prognosis. The cellular heterogeneity, origin, and tumorigenesis trajectories SCNEC remain largely unclear. We performed single-cell RNA sequencing whole-exome on tissues adjacent normal cervical from two patients diagnosed cervix. Here, we provide first comprehensive insights into composition, HPV infection-related features, gene expression profiles at resolution. Correlation analyses suggested that may originate squamous epithelial cells, this observation was validated bulk RNA-seq data external cancer. Furthermore, sex-determining region Y-box 2 (SOX2), a key transcription factor functions in direct neural differentiation, located copy number gain expressed cells both patients. Notable, distributions HPV-infected epithelium SOX2 were consistent each other. Therefore, supposed high-risk infection amplification contribute to progression small-cell

Язык: Английский

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Exploring the expression of DLL3 in gastroenteropancreatic neuroendocrine neoplasms and its potential diagnostic value

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

Опубликована: Янв. 26, 2025

Delta-like protein (DLL3) is a novel therapeutic target. DLL3 expression in gastroenteropancreatic neuroendocrine tumors (GEP-NECs) poorly understood, complicating the distinction between well-differentiated G3 (NET G3) and differentiated NEC. immunohistochemistry (IHC) was performed on 248 primary GEP-NECs, correlating with clinicopathological parameters, NE markers, PD-L1, Ki67 index, prognosis. Achaete-scute complex-like 1 (ASCL1) IHC some GEP-NECs. conducted 36 GEP-NETs, 29 gastric adenocarcinomas (GACs), metastatic (9 lymph node metastases 19 distant metastases). rates were 54.8% GEP-NECs at site, associated small cell carcinoma (SCNEC) (p < 0.001), chemotherapy before baseline = 0.015), least two markers 0.048). similar to that of tumors. Expression NET G1, G2, G3, GACs 0%, 15.8%, respectively, highlighting as powerful tool for identifying related ASCL1 especially SCNEC. It not correlated progression-free survival (PFS) or overall survival(OS), regardless cutoff value (1%, 50%, 75%). In conclusion, targeted therapy may offer potential treatment NEC digestive system, although further studies are needed validate its efficacy.

Язык: Английский

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Radiotherapy versus no radiotherapy for rectal neuroendocrine carcinoma patients treated with surgery and chemotherapy: a population-based cohort study

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Background: Chemotherapy is regularly recommended for surgically rectal neuroendocrine carcinoma (NEC) patients. However, the additional benefit of perioperative radiotherapy these patients unclear to date. This study aims evaluate outcome in NECs who treated with surgery and chemotherapy. Methods: This a retrospective controlled based on SEER database. Propensity score matching (PSM) was applied reduce baseline bias. Rectal underwent surgical resection plus chemotherapy or without were extracted from According whether receiving radiotherapy, divided into two cohorts: radiation treatment (RT) group non-RT group. Overall survival (OS) measured assess clinical benefits RT. Kaplan–Meier analysis, univariable multivariable regression analysis applied. Results: A total 666 eligible finally enrolled. The difference OS remained significant both before after PSM. Subgroup analyses revealed significantly better results stage Ⅱ, Ⅲ even Ⅳ received (all p<0.05). showed that associated (HR 0.54; 95% CI 0.45 0.65; p< 0.001), together distant metastasis. These consistent (both ​Conclusions: Radiotherapy an independent favorable prognostic factor NECs. addition might improve outcome. In future, well-designed prospective studies are needed potential role managing resectable NEC.

Язык: Английский

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Molecular Subtypes and Targeted Therapeutic Strategies in Small Cell Lung Cancer: Advances, Challenges, and Future Perspectives

Molecules, Год журнала: 2025, Номер 30(8), С. 1731 - 1731

Опубликована: Апрель 12, 2025

Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid progression, early metastasis, and high recurrence rates. Historically considered homogeneous disease, recent multi-omic studies have revealed distinct molecular subtypes driven lineage-defining transcription factors, including ASCL1, NEUROD1, POU2F3, YAP1, as well an inflamed subtype (SCLC-I). These exhibit unique therapeutic vulnerabilities, thereby paving the way for precision medicine targeted therapies. Despite advances in classification, tumor heterogeneity, plasticity, therapy resistance continue to hinder clinical success treating SCLC patients. To this end, novel strategies are being explored, BCL2 inhibitors, DLL3-targeting agents, Aurora kinase PARP epigenetic modulators. Additionally, immune checkpoint inhibitors (ICIs) show promise, particularly immune-enriched of Hence, deeper understanding characteristics, evolution, regulatory mechanisms subtype-specific factors crucial rationally optimizing therapy. This knowledge not only facilitates identification targets, but also provides foundation overcoming developing personalized combination treatment strategies. In future, integration data, dynamic monitoring, approaches expected further advance translation therapies, ultimately improving patient survival outcomes.

Язык: Английский

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Immunohistochemical investigation of the transcription factor PROX1 emphasizing on neuroendocrine neoplasms

Medical Molecular Morphology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 15, 2025

Язык: Английский

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Multi-omics analysis constructs a novel neuroendocrine prostate cancer classifier and classification system

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

Опубликована: Апрель 22, 2025

Neuroendocrine prostate cancer (NEPC), a subtype of (PCa) with poor prognosis and high heterogeneity, currently lacks accurate markers. This study aims to identify robust NEPC classifier provide new perspectives for resolving intra- tumoral heterogeneity. Multi-omics analysis included 19 bulk transcriptomics, 14 single-cell 1 spatial 16 published NE signatures 10 cellular experiments combined multiple machine learning algorithms construct novel classification. A comprehensive atlas was created from 70 samples, comprising 196,309 cells, among which 9% were identified as cells. Within this framework in combination total 100 high-quality NE-specific feature genes differentiated into NEPup sig NEPdown sig. The random forest (RF) algorithm proved be the most effective NEPC, leading establishment NEP100 model, demonstrated validation across various datasets. In clinical settings, use model can greatly improve diagnostic prognostic prediction NEPC. Hierarchical clustering based on revealed four distinct subtypes, designated VR_O, Prol_N, Prol_P, EMT_Y, each presented unique biological characteristics. allows us select different targeted therapeutic strategies subtypes phenotypic pathways. Notably, expression correlated positively neuroendocrine differentiation disease progression, while VR-NE phenotype dominated by VR_O cells indicated propensity treatment resistance. Furthermore, AMIGO2, component signature, associated chemotherapy resistance prognosis, indicating that it is pivotal target future strategies. used multi-omics classification system. provides clinically actionable diagnosis subtyping.

Язык: Английский

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Dissecting small cell carcinoma of the esophagus ecosystem by single-cell transcriptomic analysis

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Май 15, 2025

Язык: Английский

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Metabolic changes in neuroendocrine neoplasms

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Май 16, 2025

Neuroendocrine neoplasms (NENs) are a group of highly heterogeneous originating from neuroendocrine cells with gradually increased incidence. Metabolic change is one the recognized markers tumor progression, which has been extensively and systematically studied in other malignant tumors. However, metabolic NENs relatively poorly studied, systematic reviews lacking. We reviewed relationship between changes aspects glucose metabolism, lipid syndrome, amino acid metabolism metabolomics, discussed potential therapeutic strategies for NENs.

Язык: Английский

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Basal cell of origin resolves neuroendocrine-tuft lineage plasticity in cancer

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 15, 2024

Summary paragraph Neuroendocrine and tuft cells are rare, chemosensory epithelial lineages defined by expression of ASCL1 POU2F3 transcription factors, respectively 1,2 . cancers, including small cell lung cancer (SCLC), frequently display tuft-like subsets, a feature linked to poor patient outcomes 3–13 The mechanisms driving neuroendocrine–tuft tumour heterogeneity, the origins cancers unknown. Using multiple genetically-engineered animal models SCLC, we demonstrate that basal origin (but not accepted neuroendocrine origin) generates neuroendocrine–tuft-like tumours highly recapitulate human SCLC. Single-cell clonal analyses basal-derived SCLC further uncovers unexpected transcriptional states lineage trajectories underlying plasticity. Uniquely in cells, introduction genetic alterations enriched high MYC, PTEN loss, suppression, cooperate promote tumours. Transcriptomics 944 SCLCs reveal basal-like subset tuft-ionocyte-like state altogether remarkable conservation between normal injury response 14–18 Together, these data suggest is plausible for other neuroendocrine-tuft can explain heterogeneity—offering new insights targeting

Язык: Английский

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