Sympathetic Neurons Promote Small Cell Lung Cancer through the β2-Adrenergic Receptor

Tala Fnu; Peiguo Shi; Wanwei Zhang; Sanny S W Chung; Christopher B Damoci; Yinshan Fang; Qi-Yue Chen; Anjali Saqi; Yuefeng Huang; Xuebing Wu; Chao Lu; Dian Yang; Timothy C Wang; Jianwen Que

doi:10.1158/2159-8290.CD-24-0718

Sympathetic Neurons Promote Small Cell Lung Cancer through the β2-Adrenergic Receptor

Cancer Discov. 2025 Mar 3;15(3):616-632. doi: 10.1158/2159-8290.CD-24-0718.

Authors

Tala Fnu^{1

2}, Peiguo Shi^{3

4}, Wanwei Zhang⁵, Sanny S W Chung^{1

2}, Christopher B Damoci², Yinshan Fang^{1

2}, Qi-Yue Chen^{1

2

6

7

8}, Anjali Saqi⁹, Yuefeng Huang⁵, Xuebing Wu^{3

4}, Chao Lu^{2

10}, Dian Yang^{4

11}, Timothy C Wang^{2

12}, Jianwen Que^{1

2

12}

Affiliations

¹ Department of Medicine, Columbia Center for Human Development, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.
² Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.
³ Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, New York.
⁴ Department of System Biology, Columbia University Irving Medical Center, New York, New York.
⁵ Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.
⁶ Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, P.R. China.
⁷ Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, P.R. China.
⁸ Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, P.R. China.
⁹ Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York.
¹⁰ Department of Genetics and Development, Columbia University Irving Medical Center, New York, New York.
¹¹ Department of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, New York.
¹² Division of Digestive and Liver Disease, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.

PMID: 39513738
PMCID: PMC11875942 (available on 2025-09-03)
DOI: 10.1158/2159-8290.CD-24-0718

Abstract

SCLC is highly aggressive, with limited effective treatment options. We show that ablating sympathetic nerves or inhibiting the ADRB2 receptor slows SCLC progression and prolongs survival in mice. Additionally, ADRB2 inhibition reduces the growth of human SCLC organoids and xenografts by disrupting PKA signaling, identifying a new therapeutic target.

MeSH terms

Animals
Cell Line, Tumor
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / metabolism
Lung Neoplasms* / pathology
Mice
Receptors, Adrenergic, beta-2* / genetics
Receptors, Adrenergic, beta-2* / metabolism
Signal Transduction
Small Cell Lung Carcinoma* / drug therapy
Small Cell Lung Carcinoma* / metabolism
Small Cell Lung Carcinoma* / pathology
Xenograft Model Antitumor Assays

Substances

Receptors, Adrenergic, beta-2

Abstract

MeSH terms

Substances

Grants and funding