Dopamine D(2) receptor agonists abrogate neuroendocrine tumour angiogenesis to inhibit chemotherapy-refractory small cell lung cancer progression Journal Article

   

Authors:	Alam, S. K.; Pandit, A.; Wang, L.; Mortazavi Farsani, S. S.; Thiele, B. A.; Manoj, P.; Aubry, M. C.; Verma, V.; Rudin, C. M.; Lo, Y. C.; Hoeppner, L. H.
Article Title:	Dopamine D(2) receptor agonists abrogate neuroendocrine tumour angiogenesis to inhibit chemotherapy-refractory small cell lung cancer progression
Abstract:	Small cell lung cancer (SCLC) is difficult to treat due to its aggressiveness, early metastasis, and rapid development of resistance to chemotherapeutic agents. Here, we show that treatment with a dopamine D2 receptor (D2R) agonist reduces tumour angiogenesis in multiple in vivo xenograft models of human SCLC, thereby reducing SCLC progression. An FDA-approved D2R agonist, cabergoline, also sensitized chemotherapy-resistant SCLC tumours to cisplatin and etoposide in patient-derived xenograft models of acquired chemoresistance in mice. Ex vivo, D2R agonist treatment decreased tumour angiogenesis through increased apoptosis of tumour-associated endothelial cells, creating a less favourable tumour microenvironment that limited cancer cell proliferation. In paired SCLC patient-derived specimens, D2R was expressed by tumour-associated endothelial cells obtained before treatment, but D2R was downregulated in SCLC tumours that had acquired chemoresistance. D2R agonist treatment of chemotherapy-resistant specimens restored expression of D2R. Activation of dopamine signalling is thus a new strategy for inhibiting angiogenesis in SCLC and potentially for combatting chemotherapy-refractory SCLC progression. © The Author(s) 2025.
Keywords:	immunohistochemistry; controlled study; human tissue; protein expression; human cell; cisplatin; cancer growth; nonhuman; cancer staging; flow cytometry; cell proliferation; animal cell; mouse; animal; metabolism; animals; mice; animal tissue; apoptosis; tumor volume; etoposide; lung neoplasms; animal experiment; animal model; food and drug administration; drug effect; drug resistance; drug screening; pathology; drug resistance, neoplasm; xenograft model antitumor assays; cell line, tumor; angiogenesis; neovascularization, pathologic; vascularization; neuroendocrine tumor; endothelium cell; lung tumor; nude mouse; mice, nude; disease progression; cancer cell; tumor cell line; down regulation; tumor growth; drug therapy; ex vivo study; antiangiogenic activity; neovascularization (pathology); disease exacerbation; bioluminescence; dopamine; neuroendocrine tumors; small cell lung cancer; small cell lung carcinoma; tumor microenvironment; antiproliferative activity; dopamine 2 receptor; tumor weight; dopamine receptor stimulating agent; receptors, dopamine d2; humans; human; female; article; dopamine agonists; cabergoline; organoid; tunel assay; quinpirole
Journal Title:	Cell Death & Disease
Volume:	16
ISSN:	2041-4889
Publisher:	Nature Publishing Group
Date Published:	2025-05-09
Start Page:	370
Language:	English
DOI:	10.1038/s41419-025-07693-y
PUBMED:	40346068
PROVIDER:	scopus
PMCID:	PMC12064713
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105004674689&doi=10.1038%2fs41419-025-07693-y&partnerID=40&md5=439268e46016f928411ff8c6ac0886fd
Notes:	Article -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/225413