Biochemical and Biophysical Research Communications, Год журнала: 2024, Номер 745, С. 151238 - 151238
Опубликована: Дек. 25, 2024
Язык: Английский
Cancer Cell, Год журнала: 2024, Номер 42(8), С. 1336 - 1351.e9
Опубликована: Июль 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.
Язык: Английский
Процитировано
15
Trends in cancer, Год журнала: 2024, Номер 10(10), С. 935 - 946
Опубликована: Авг. 19, 2024
Язык: Английский
Процитировано
8
Cancer Discovery, Год журнала: 2025, Номер 15(1), С. 8 - 10
Опубликована: Янв. 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
Язык: Английский
Процитировано
0
Nature reviews. Cancer, Год журнала: 2025, Номер unknown
Опубликована: Апрель 10, 2025
Язык: Английский
Процитировано
0
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
Процитировано
0
Current Opinion in Oncology, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 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.
Язык: Английский
Процитировано
2
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
Процитировано
2
Cancer Cell, Год журнала: 2024, Номер 42(8), С. 1326 - 1328
Опубликована: Авг. 1, 2024
Язык: Английский
Процитировано
1
Modern Pathology, Год журнала: 2024, Номер unknown, С. 100674 - 100674
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
0
Biochemical and Biophysical Research Communications, Год журнала: 2024, Номер 745, С. 151238 - 151238
Опубликована: Дек. 25, 2024
Язык: Английский
Процитировано
0