{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T11:48:50Z","timestamp":1775994530349,"version":"3.50.1"},"posted":{"date-parts":[[2025,4,14]]},"group-title":"Cancer Biology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Malignant pleural mesothelioma (MPM) is a rare thoracic cancer associated with poor prognosis and low survival rates. In solid cancers, repurposed dopamine receptor antagonists have been shown to have anti-cancer effects. Moreover, in combination with radiotherapy, quetiapine (QTP), a dopamine (D) 2\/3 receptor antagonist, has been shown to interfere with self-renewal capacity in glioma-initiating cells and increase survival in mouse models of glioblastoma. In this study we explore combined treatment effects in MPM.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Using mesothelioma cell lines, MSTO-211H, H2052, and H2452, and a MSTO-211H-derived orthotopic xenograft mouse model of MPM we examined how QTP combined with radiation affects mesothelioma-initiating cells (MICs)\n                    <jats:italic>in vitro<\/jats:italic>\n                    and survival\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Subsequently, bulk and single cell RNA sequencing was used to characterize the transcriptomic landscape of MSTO-211H treated with combined radiation and QTP.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    We demonstrate that combining QTP with radiation reduces MIC self-renewal capacity and stem cell frequency.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , this combination therapy significantly extends the median survival of mesothelioma-bearing mice. Clonogenic survival assays revealed that QTP does not enhance radiosensitivity in the tested mesothelioma cell lines. Sequencing data revealed, combined treatment downregulated cell cycle and proliferation pathways, depleted cancer stem cells, and increased cellular senescence.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Taken together, our study highlights the therapeutic potential of radiation with QTP in the treatment of MPM.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.04.08.647821","type":"posted-content","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T09:15:11Z","timestamp":1744622111000},"source":"Crossref","is-referenced-by-count":0,"title":["Combined quetiapine and radiation therapy approach to treat mesothelioma-initiating cells and increase survival in a mouse model of mesothelioma"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-3253","authenticated-orcid":false,"given":"Anjelica","family":"Cardenas","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn","family":"Arambula","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8788-7278","authenticated-orcid":false,"given":"Linda","family":"Azizi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Sutlief","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kruttika","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Saki","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"He","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4067-9751","authenticated-orcid":false,"given":"Frank","family":"Pajonk","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA"},{"name":"Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA"},{"name":"Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041204100015000_2025.04.08.647821v1.1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.0901196"},{"key":"2026041204100015000_2025.04.08.647821v1.2","unstructured":"Society AC . 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