{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:22:06Z","timestamp":1789590126812,"version":"build-2803163510"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173280"],"award-info":[{"award-number":["82173280"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004912","name":"Sichuan University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004912","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013365","name":"West China Hospital, Sichuan University","doi-asserted-by":"publisher","award":["ZYJC21016"],"award-info":[{"award-number":["ZYJC21016"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine &amp; Pharmacotherapy"],"published-print":{"date-parts":[[2023,12]]},"DOI":"10.1016\/j.biopha.2023.115665","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T02:59:51Z","timestamp":1696993191000},"page":"115665","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Pimavanserin tartrate induces apoptosis and cytoprotective autophagy and synergizes with chemotherapy on triple negative breast cancer"],"prefix":"10.1016","volume":"168","author":[{"given":"Yiqian","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianrui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qisi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengsen","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7939-9995","authenticated-orcid":false,"given":"Yong","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.biopha.2023.115665_bib1","doi-asserted-by":"crossref","unstructured":"Akram M., Iqbal M., Daniyal M., Khan A.U.J.Br Awareness and current knowledge of breast cancer. 2017;50:1\u201323.","DOI":"10.1186\/s40659-017-0140-9"},{"issue":"10074","key":"10.1016\/j.biopha.2023.115665_bib2","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/S0140-6736(16)31891-8","article-title":"Breast cancer","volume":"389","author":"Harbeck","year":"2017","journal-title":"Lancet (Lond., Engl.)"},{"key":"10.1016\/j.biopha.2023.115665_bib3","doi-asserted-by":"crossref","unstructured":"Rakha E.A., El-Sayed M.E., Green A.R., Lee A.H.S., Robertson J.F., Ellis I.O. Prognostic markers in triple-negative breast cancer. 2007;109(1):25\u201332. doi:\u3008https:\/\/doi.org\/10.1002\/cncr.22381\u3009.","DOI":"10.1002\/cncr.22381"},{"key":"10.1016\/j.biopha.2023.115665_bib4","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.bpobgyn.2019.11.006","article-title":"Breast cancer prevention in high-risk women","volume":"65","author":"Thorat","year":"2020","journal-title":"Best. Pract. Res. Clin. Obstet. Gynaecol."},{"issue":"3","key":"10.1016\/j.biopha.2023.115665_bib5","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1001\/jama.2018.19323","article-title":"Breast cancer treatment: a review","volume":"321","author":"Waks","year":"2019","journal-title":"Jama"},{"issue":"3","key":"10.1016\/j.biopha.2023.115665_bib6","doi-asserted-by":"crossref","first-page":"900","DOI":"10.20892\/j.issn.2095-3941.2020.0523","article-title":"Breast cancer incidence and mortality in women in China: temporal trends and projections to 2030","volume":"18","author":"Lei","year":"2021","journal-title":"Cancer Biol. Med."},{"key":"10.1016\/j.biopha.2023.115665_bib7","doi-asserted-by":"crossref","first-page":"12619","DOI":"10.1038\/ncomms12619","article-title":"Centromere and kinetochore gene misexpression predicts cancer patient survival and response to radiotherapy and chemotherapy","volume":"7","author":"Zhang","year":"2016","journal-title":"Nat. Commun."},{"issue":"4","key":"10.1016\/j.biopha.2023.115665_bib8","doi-asserted-by":"crossref","first-page":"853","DOI":"10.4103\/0973-1482.139267","article-title":"An overview of doxorubicin formulations in cancer therapy","volume":"10","author":"Rivankar","year":"2014","journal-title":"J. Cancer Res. Ther."},{"key":"10.1016\/j.biopha.2023.115665_bib9","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jconrel.2016.06.003","article-title":"A safe, simple and efficient doxorubicin prodrug hybrid micelle for overcoming tumor multidrug resistance and targeting delivery","volume":"235","author":"Bao","year":"2016","journal-title":"J. Control. Release: Off. J. Control. Release Soc."},{"issue":"2","key":"10.1016\/j.biopha.2023.115665_bib10","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/1097-0142(197308)32:2<302::AID-CNCR2820320205>3.0.CO;2-2","article-title":"A clinicopathologic analysis of adriamycin cardiotoxicity","volume":"32","author":"Lefrak","year":"1973","journal-title":"Cancer"},{"issue":"2","key":"10.1016\/j.biopha.2023.115665_bib11","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1124\/jpet.111.183681","article-title":"Amelioration of doxorubicin-induced cardiotoxicity by an anticancer-antioxidant dual-function compound, HO-3867","volume":"339","author":"Dayton","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"4","key":"10.1016\/j.biopha.2023.115665_bib12","doi-asserted-by":"crossref","first-page":"479","DOI":"10.6004\/jnccn.2020.7554","article-title":"Role of immunotherapy in triple-negative breast cancer","volume":"18","author":"Keenan","year":"2020","journal-title":"J. Natl. Compr. Cancer Netw.: JNCCN"},{"issue":"4","key":"10.1016\/j.biopha.2023.115665_bib13","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s40262-017-0587-4","article-title":"PARP inhibitors in the treatment of triple-negative breast cancer","volume":"57","author":"Geenen","year":"2018","journal-title":"Clin. Pharmacokinet."},{"issue":"4","key":"10.1016\/j.biopha.2023.115665_bib14","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1158\/0008-5472.CAN-15-1233","article-title":"Penfluridol: an antipsychotic agent suppresses metastatic tumor growth in triple-negative breast cancer by inhibiting integrin signaling axis","volume":"76","author":"Ranjan","year":"2016","journal-title":"Cancer Res."},{"issue":"1","key":"10.1016\/j.biopha.2023.115665_bib15","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/ijc.24813","article-title":"Cytotoxic effects of antipsychotic drugs implicate cholesterol homeostasis as a novel chemotherapeutic target","volume":"126","author":"Wiklund","year":"2010","journal-title":"Int. J. Cancer"},{"issue":"20","key":"10.1016\/j.biopha.2023.115665_bib16","doi-asserted-by":"crossref","first-page":"32960","DOI":"10.18632\/oncotarget.16515","article-title":"Penfluridol suppresses glioblastoma tumor growth by Akt-mediated inhibition of GLI1","volume":"8","author":"Ranjan","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.biopha.2023.115665_bib17","doi-asserted-by":"crossref","first-page":"26165","DOI":"10.1038\/srep26165","article-title":"Penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis","volume":"6","author":"Ranjan","year":"2016","journal-title":"Sci. Rep."},{"issue":"29","key":"10.1016\/j.biopha.2023.115665_bib18","doi-asserted-by":"crossref","first-page":"47632","DOI":"10.18632\/oncotarget.17425","article-title":"Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth","volume":"8","author":"Ranjan","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.biopha.2023.115665_bib19","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.semcancer.2019.10.007","article-title":"Repurposing antipsychotics of the diphenylbutylpiperidine class for cancer therapy","volume":"68","author":"Shaw","year":"2021","journal-title":"Semin. Cancer Biol."},{"issue":"10","key":"10.1016\/j.biopha.2023.115665_bib20","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1007\/s11064-014-1293-3","article-title":"On the discovery and development of pimavanserin: a novel drug candidate for Parkinson's psychosis","volume":"39","author":"Hacksell","year":"2014","journal-title":"Neurochem. Res."},{"issue":"3","key":"10.1016\/j.biopha.2023.115665_bib21","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1017\/S1092852917000736","article-title":"Pimavanserin for the treatment of Parkinson's disease psychosis: number needed to treat, number needed to harm, and likelihood to be helped or harmed","volume":"23","author":"Citrome","year":"2018","journal-title":"CNS Spectr."},{"issue":"6","key":"10.1016\/j.biopha.2023.115665_bib22","first-page":"368","article-title":"imavanserin (Nuplazid): a treatment for hallucinations and delusions associated with Parkinson's disease","volume":"42","author":"Cruz","year":"2017","journal-title":"P T: Peer-Rev. J. Formul. Manag."},{"issue":"4","key":"10.1016\/j.biopha.2023.115665_bib23","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1017\/S1092852916000407","article-title":"Mechanism of action of pimavanserin in Parkinson's disease psychosis: targeting serotonin 5HT2A and 5HT2C receptors","volume":"21","author":"Stahl","year":"2016","journal-title":"CNS Spectr."},{"issue":"11","key":"10.1016\/j.biopha.2023.115665_bib24","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1038\/s41401-021-00724-2","article-title":"Identification of pimavanserin tartrate as a potent Ca(2+)-calcineurin-NFAT pathway inhibitor for glioblastoma therapy","volume":"42","author":"Liu","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.biopha.2023.115665_bib25","unstructured":"Li B., Yang J., Qi J.J.I.J.C.E.M.. Pimavanserin inhibits growth and invasion of bladder cancer cells. 2019;12(8):10342\u201310349."},{"issue":"12_Supplement","key":"10.1016\/j.biopha.2023.115665_bib26","doi-asserted-by":"crossref","DOI":"10.1158\/1538-7445.AM2022-1559","article-title":"Abstract 1559: repurposing of pimavanserin tartrate for the treatment of glioblastoma","volume":"82","author":"Zabel","year":"2022","journal-title":"Cancer Res."},{"key":"10.1016\/j.biopha.2023.115665_bib27","doi-asserted-by":"crossref","unstructured":"Ramachandran S., Gaikwad S., Srivastava SKJCR. Pimavanserin suppresses the growth of medulloblastoma by inhibiting Lyn\/STAT3\/MBSC signaling axis. 2022;82(12_Supplement):3896\u20133896.","DOI":"10.1158\/1538-7445.AM2022-3896"},{"issue":"22","key":"10.1016\/j.biopha.2023.115665_bib28","first-page":"13","article-title":"Pimavanserin: a novel autophagy modulator for pancreatic cancer treatment","author":"Ramachandran","year":"2021","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.biopha.2023.115665_bib29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.omto.2020.08.019","article-title":"Repurposing pimavanserin, an anti-Parkinson drug for pancreatic cancer therapy","volume":"19","author":"Ramachandran","year":"2020","journal-title":"Mol. Ther. Oncolytics"},{"key":"10.1016\/j.biopha.2023.115665_bib30","doi-asserted-by":"crossref","unstructured":"Liu N., Sun Q., Xu H., et al. Hyperuricemia induces lipid disturbances mediated by LPCAT3 upregulation in the liver. 2020;34(10):13474\u201313493. doi:\u3008https:\/\/doi.org\/10.1096\/fj.202000950R\u3009.","DOI":"10.1096\/fj.202000950R"},{"issue":"7","key":"10.1016\/j.biopha.2023.115665_bib31","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1142\/S0192415X17500835","article-title":"Combination of cinobufacini and doxorubicin increases apoptosis of hepatocellular carcinoma cells through the fas- and mitochondria-mediated pathways","volume":"45","author":"Xia","year":"2017","journal-title":"Am. J. Chin. Med."},{"issue":"3","key":"10.1016\/j.biopha.2023.115665_bib32","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.58.3.10","article-title":"Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies","volume":"58","author":"Chou","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.biopha.2023.115665_bib33","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.canlet.2018.04.039","article-title":"Repurposing drugs for glioblastoma: from bench to bedside","volume":"428","author":"Basso","year":"2018","journal-title":"Cancer Lett."},{"issue":"9","key":"10.1016\/j.biopha.2023.115665_bib34","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.tips.2013.06.005","article-title":"Cancer drug discovery by repurposing: teaching new tricks to old dogs","volume":"34","author":"Gupta","year":"2013","journal-title":"Trends Pharmacol. Sci."},{"issue":"5","key":"10.1016\/j.biopha.2023.115665_bib35","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41422-019-0164-5","article-title":"The molecular machinery of regulated cell death","volume":"29","author":"Tang","year":"2019","journal-title":"Cell Res."},{"issue":"5","key":"10.1016\/j.biopha.2023.115665_bib36","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1093\/emboj\/17.5.1268","article-title":"Alphaviruses induce apoptosis in Bcl-2-overexpressing cells: evidence for a caspase-mediated, proteolytic inactivation of Bcl-2","volume":"17","author":"Grandgirard","year":"1998","journal-title":"EMBO J."},{"issue":"5345","key":"10.1016\/j.biopha.2023.115665_bib37","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1126\/science.278.5345.1966","article-title":"Conversion of Bcl-2 to a Bax-like death effector by caspases","volume":"278","author":"Cheng","year":"1997","journal-title":"Sci. (N. Y., NY)"},{"issue":"47","key":"10.1016\/j.biopha.2023.115665_bib38","doi-asserted-by":"crossref","first-page":"31437","DOI":"10.1074\/jbc.273.47.31437","article-title":"Nitric oxide suppression of apoptosis occurs in association with an inhibition of Bcl-2 cleavage and cytochrome c release","volume":"273","author":"Kim","year":"1998","journal-title":"J. Biol. Chem."},{"issue":"6","key":"10.1016\/j.biopha.2023.115665_bib39","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrm830","article-title":"IAP proteins: blocking the road to death's door","volume":"3","author":"Salvesen","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"4","key":"10.1016\/j.biopha.2023.115665_bib40","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.1745-7270.2008.00407.x","article-title":"Inhibitor of apoptosis proteins and apoptosis","volume":"40","author":"Wei","year":"2008","journal-title":"Acta Biochim. Et. Biophys. Sin."},{"issue":"11","key":"10.1016\/j.biopha.2023.115665_bib41","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/nrc1736","article-title":"Promoting apoptosis as a strategy for cancer drug discovery","volume":"5","author":"Fesik","year":"2005","journal-title":"Nat. Rev. Cancer"},{"issue":"6","key":"10.1016\/j.biopha.2023.115665_bib42","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.freeradbiomed.2009.12.022","article-title":"Reactive oxygen species, cellular redox systems, and apoptosis","volume":"48","author":"Circu","year":"2010","journal-title":"Free Radic. Biol. Med."},{"issue":"5","key":"10.1016\/j.biopha.2023.115665_bib43","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1023\/A:1009616228304","article-title":"Role of reactive oxygen species (ROS) in apoptosis induction","volume":"5","author":"Simon","year":"2000","journal-title":"Apoptosis: Int. J. Program. Cell Death"},{"key":"10.1016\/j.biopha.2023.115665_bib44","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ymeth.2014.11.021","article-title":"LC3- and p62-based biochemical methods for the analysis of autophagy progression in mammalian cells","volume":"75","author":"Jiang","year":"2015","journal-title":"Methods (San. Diego, Calif.)"},{"issue":"1","key":"10.1016\/j.biopha.2023.115665_bib45","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1038\/s41467-022-30258-y","article-title":"Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors","volume":"13","author":"Beyett","year":"2022","journal-title":"Nat. Commun."},{"issue":"11","key":"10.1016\/j.biopha.2023.115665_bib46","doi-asserted-by":"crossref","DOI":"10.3390\/cancers11111623","article-title":"Destined to die: apoptosis and pediatric cancers","volume":"11","author":"Choo","year":"2019","journal-title":"Cancers"}],"container-title":["Biomedicine &amp; Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332223014634?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332223014634?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:31:42Z","timestamp":1779917502000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0753332223014634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":46,"alternative-id":["S0753332223014634"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2023.115665","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pimavanserin tartrate induces apoptosis and cytoprotective autophagy and synergizes with chemotherapy on triple negative breast cancer","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2023.115665","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Author(s). Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"115665"}}