Stimulation of cGAS-STING pathway as a challenge in the treatment of small cell lung cancer: a feasible strategy? DOI Creative Commons
Giulia Miglietta, Marco Russo, Giovanni Capranico

et al.

British Journal of Cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 31, 2024

Abstract Lung cancer has a significant incidence among the population and, unfortunately, an unfavourable prognosis in most cases. The World Health Organization (WHO) classifies lung tumours into two subtypes based on their phenotype: Non-Small Cell Cancer (NSCLC) and Small (SCLC). SCLC treatment, despite advances chemotherapy radiotherapy, is often unsuccessful for recurrence highlighting need to develop novel therapeutic strategies. In this review, we describe genetic landscape tumour microenvironment that characterize pathological processes of how they are responsible immune evasion. immunosuppressive mechanisms engaged critical factors understand failure immunotherapy conversely, suggest new signalling pathways, such as cGAS/STING, should be investigated possible targets stimulate innate response subtype cancer. full comprehension immunity cells thus crucial open challenges successful treating improving patient outcomes.

Language: Английский

Emerging advances in defining the molecular and therapeutic landscape of small-cell lung cancer DOI
Triparna Sen, Nobuyuki Takahashi,

Subhamoy Chakraborty

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(8), P. 610 - 627

Published: July 4, 2024

Language: Английский

Citations

24
Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities DOI Creative Commons
Nanhao Yin, Xintong Li, Xuanwei Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 22, 2024

Abstract Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment, but challenges related to resistance toxicity still remain. Due the advancement of immuno-oncology, an increasing number novel immunoregulatory targets mechanisms are being revealed, with relevant therapies promising improve clinical immunotherapy in foreseeable future. Therefore, comprehending larger picture is important. In this review, we analyze summarize current landscape preclinical translational mechanistic research, drug development, trials that brought about next-generation pharmacological anti-cancer agents candidates beyond classical immune checkpoint inhibitors. Along further clarification immunobiology advances antibody engineering, targeting additional inhibitory checkpoints, including LAG-3, TIM-3, TIGIT, CD47, B7 family members becoming important part research discovery, as structurally functionally optimized agonists co-stimulatory molecules T cells. Exemplified bispecific cell engagers, newly emerging bi-specific multi-specific antibodies can provide considerable benefits. Next-generation also include epigenetic drugs cytokine-based therapeutics. Cell therapies, vaccines, oncolytic viruses not covered review. This comprehensive review might aid development fastest possible adoption effective immuno-oncology modalities for benefit patients.

Language: Английский

Citations

20
Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer DOI Creative Commons
Leslie Duplaquet, Kevin Kam Fung So,

Alexander W. Ying

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(8), P. 1352 - 1369.e13

Published: July 18, 2024

Small cell lung cancers (SCLCs) are composed of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLCs, ∼12% all cases, uniquely dependent on POU2F3 itself; as such, approaches to attenuate expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators SCLC proliferation, we define mSWI/SNF complexes top dependencies specific SCLC. Notably, chemical disruption ATPase activity attenuates proliferation while non-canonical BAF (ncBAF) via BRD9 degradation is effective in pure non-neuroendocrine POU2F3-SCLCs. targets maintains accessibility over gene loci central POU2F3-mediated regulatory networks. Finally, clinical-grade pharmacologic SMARCA4/2 ATPases decreases POU2F3-SCLC tumor growth increases survival vivo. These results demonstrate mSWI/SNF-mediated governance the oncogenic program suggest inhibition a strategy SCLCs.

Language: Английский

Citations

10
Spatial Transcriptome‐Wide Profiling of Small Cell Lung Cancer Reveals Intra‐Tumoral Molecular and Subtype Heterogeneity DOI Creative Commons
Zicheng Zhang,

Xujie Sun,

Yutao Liu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(31)

Published: June 19, 2024

Abstract Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth and early metastasis susceptible to treatment resistance recurrence. Understanding the intra‐tumoral spatial heterogeneity in SCLC crucial for improving patient outcomes clinically relevant subtyping. In this study, whole transcriptome‐wide analysis of 25 patients at sub‐histological resolution using GeoMx Digital Spatial Profiling technology performed. This deciphered multi‐regional heterogeneity, distinct molecular profiles, biological functions, immune features, subtypes within spatially localized histological regions. Connections between different transcript‐defined phenotypes their impact on survival therapeutic response are also established. Finally, gene signature, termed ITHtyper, based prevalence levels, which enables risk stratification from bulk RNA‐seq profiles identified. The prognostic value ITHtyper rigorously validated independent multicenter cohorts. study introduces preliminary tumor‐centric, regionally targeted transcriptome resource that sheds light previously unexplored SCLC. These findings hold promise improve tumor reclassification facilitate development personalized treatments patients.

Language: Английский

Citations

9
Integrative spatial analysis reveals tumor heterogeneity and immune colony niche related to clinical outcomes in small cell lung cancer DOI
Haiquan Chen, Chaoqiang Deng, Jian Gao

et al.

Cancer Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
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
Extensive-stage small-cell lung cancer in patients receiving atezolizumab plus carboplatin–etoposide: stratification of outcome based on a composite score that combines gene expression profiling and immune characterization of microenvironment DOI Creative Commons
Anna Tosi, M. Lorenzi, Paola Del Bianco

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(7), P. e008974 - e008974

Published: July 1, 2024

Purpose Small-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in first-line setting achieves durable benefit only patient subgroup. Thus, the identification predictive biomarkers urgent unmet medical need. Experimental design Tumor samples from naive extensive-stage (ES) SCLC patients receiving atezolizumab plus carboplatin–etoposide were analyzed by gene expression profiling and two 9-color multiplex immunofluorescence panels, characterize infiltrate subtypes. Associations tissue time-to-treatment failure (TTF), progression-free survival (PFS) overall (OS), assessed. Results 42 included. Higher exhausted CD8-related genes was independently associated longer TTF PFS while increased density B lymphocytes correlated OS. percentage M2-like macrophages close tumor cells CD8+T CD4+T risk TF survival, respectively. A lower TF, progression death higher ASCL1+tumor POU2F3 shorter survival. composite score combining genes, lymphocyte density, ASCL1 quantification CD163+macrophages cells, able stratify into high-risk low-risk groups. Conclusions In conclusion, we identified combined that can predict chemoimmunotherapy ES-SCLC patients.

Language: Английский

Citations

4
Cell-free and extrachromosomal DNA profiling of small cell lung cancer DOI Creative Commons
Roya Behrouzi, Alexandra Clipson, Kathryn Simpson

et al.

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

4
Epidemiology of Small Cell Lung Cancer in the U.S. from 2000 to 2019: A Study Utilizing the SEER Registry DOI Creative Commons
Leah Wells,

Sean Cohen,

Benjamin Brennan

et al.

JTO Clinical and Research Reports, Journal Year: 2025, Volume and Issue: 6(4), P. 100799 - 100799

Published: Jan. 20, 2025

From the late 1980s to 2000, SCLC represented a decreasing proportion of lung cancer cases in United States. Nevertheless, survival outcomes did not improve, reflecting paucity treatment advances. We sought determine whether these trends continued into more recent decades, before Food and Drug Administration approval immunotherapy for 2019, by evaluating incidence from 2000 2019 States population, with attention variance across gender racial subgroups. Using Surveillance, Epidemiology, End Results 17 database, we evaluated NSCLC 2019. Demographic, staging, data were collected patients comparing groups. The percentage among all newly diagnosed decreased 14.5% 11.8% A decrease was observed sex subgroups but earlier steeper men than women. This has resulted shift male-to-female ratio 1.14:1 0.93:1 Among subgroups, declined most slowly non-Hispanic Whites rapidly Asians Pacific Islanders. There decline limited-stage at diagnosis, 31.1% 26.4% Minimal improvement regardless patient characteristics or stage. In preimmunotherapy era both sexes narrow women outnumbering years. disease continues decline, likely because improved staging procedures. slightly remained poor, highlighting need effective strategies.

Language: Английский

Citations

0
Candidate Biomarker of Response to Immunotherapy In Small Cell Lung Cancer DOI

Yili Shen,

Zhicong Liu, Yi Chen

et al.

Current Treatment Options in Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Language: Английский

Citations

0