Identification of assembly mode of non-canonical BAF (ncBAF) chromatin remodeling complex core module DOI

Qinling Mo,

Beibei Liu,

Chunyu Liu

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 745, P. 151238 - 151238

Published: Dec. 25, 2024

Language: Английский

Targeting the mSWI/SNF complex in POU2F-POU2AF transcription factor-driven malignancies DOI Creative Commons

Tongchen He,

Lanbo Xiao, Yuanyuan Qiao

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(8), P. 1336 - 1351.e9

Published: July 18, 2024

The POU2F3-POU2AF2/3 transcription factor complex is the master regulator of tuft cell lineage and cell-like small lung cancer (SCLC). Here, we identify a specific dependence POU2F3 molecular subtype SCLC (SCLC-P) on activity mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. Treatment SCLC-P cells with proteolysis targeting chimera (PROTAC) degrader mSWI/SNF ATPases evicts its coactivators from attenuates downstream signaling. B malignancies which are dependent POU2F1/2 cofactor, POU2AF1, also sensitive to ATPase degraders, treatment leading eviction POU2AF1 IRF4 decreased signaling in multiple myeloma cells. An orally bioavailable significantly inhibits tumor growth preclinical models without signs toxicity. This study suggests that POU2F-POU2AF-driven have an intrinsic complex, representing therapeutic vulnerability.

Language: Английский

Citations

15
Small cell lung cancer profiling: an updated synthesis of subtypes, vulnerabilities, and plasticity DOI
Esther Redín, Álvaro Quintanal-Villalonga, Charles M. Rudin

et al.

Trends in cancer, Journal Year: 2024, Volume and Issue: 10(10), P. 935 - 946

Published: Aug. 19, 2024

Language: Английский

Citations

8
Atypical Small Cell Lung Cancer: A New Malignancy Characterized by Chromothripsis, Carcinoid Tumors, and Wild-type RB1 and TP53 DOI
Urooba Nadeem, Benjamin J. Drapkin

Cancer Discovery, Journal Year: 2025, Volume and Issue: 15(1), P. 8 - 10

Published: Jan. 13, 2025

Summary: Small cell lung cancer (SCLC) and pulmonary carcinoid tumors are traditionally seen as unrelated, with SCLC linked to smoking characterized by biallelic loss of RB1 TP53 rapid progression. Rekhtman colleagues upend these assumptions discovering an “atypical” that arises in nonsmokers intact loci, chromothripsis-induced oncogene amplifications on extrachromosomal DNA, frequent synchronous tumors. See related article et al., p. 83

Language: Английский

Citations

0
Challenges of small cell lung cancer heterogeneity and phenotypic plasticity DOI
Kathryn Simpson, Dominic G. Rothwell, Fiona Blackhall

et al.

Nature reviews. Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Language: Английский

Citations

0
Molecular Subtypes and Targeted Therapeutic Strategies in Small Cell Lung Cancer: Advances, Challenges, and Future Perspectives DOI Creative Commons
Daoyuan Huang, Jingchao Wang, Li Chen

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(8), P. 1731 - 1731

Published: April 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.

Language: Английский

Citations

0
Recent advances in immunotherapy for small cell lung cancer DOI
Ziyuan Ren,

Shijie Shang,

Dawei Chen

et al.

Current Opinion in Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

This review aims to provide an overview of recent advances in immunotherapy for small cell lung cancer (SCLC), with a focus on the current status immune checkpoint inhibitors (ICIs), novel combination strategies, and key biomarkers.

Language: Английский

Citations

2
Basal cell of origin resolves neuroendocrine-tuft lineage plasticity in cancer DOI Creative Commons
Abbie S. Ireland,

Sarah B. Hawgood,

Dong Xie

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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

Language: Английский

Citations

2
Transcription factor dependencies identify BAF-dependent cancers DOI
Helen M. McRae, Diana C. Hargreaves

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(8), P. 1326 - 1328

Published: Aug. 1, 2024

Language: Английский

Citations

1
Analysis of ASCL1/NEUROD1/POU2F3/YAP1 Yields Novel Insights for the Diagnosis of Olfactory Neuroblastoma and Identifies Sinonasal Tuft Cell-like Carcinoma DOI

Christopher A. Febres‐Aldana,

M Elsayad,

Maelle Saliba

et al.

Modern Pathology, Journal Year: 2024, Volume and Issue: unknown, P. 100674 - 100674

Published: Nov. 1, 2024

Language: Английский

Citations

0
Identification of assembly mode of non-canonical BAF (ncBAF) chromatin remodeling complex core module DOI

Qinling Mo,

Beibei Liu,

Chunyu Liu

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 745, P. 151238 - 151238

Published: Dec. 25, 2024

Language: Английский

Citations

0