{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T04:26:32Z","timestamp":1766377592935,"version":"3.37.3"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","issue":"13","funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT) National Funds","doi-asserted-by":"publisher","award":["IF\/00092\/2014\/CP1255\/CT0004","UIDB\/4255\/2020","SFRH\/BD\/140734\/2018"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004","UIDB\/4255\/2020","SFRH\/BD\/140734\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CDM"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec>\n<jats:title>:<\/jats:title>\n<jats:p>Antimalarial drugs from different classes have demonstrated anticancer effects in different types of cancer\ncells, but their complete mode of action in cancer remains unknown. Recently, several studies reported the important\nrole of palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme, as the molecular target of chloroquine and its\nderivates in cancer. It was also found that PPT1 is overexpressed in different types of cancer, such as breast, colon,\netc. Our group has found a synergistic interaction between antimalarial drugs, such as mefloquine, artesunate and\nchloroquine and antineoplastic drugs in breast cancer cells, but the mechanism of action was not determined. Here,\nwe describe the importance of autophagy and lysosomal inhibitors in tumorigenesis and hypothesize that other antimalarial\nagents besides chloroquine could also interact with PPT1 and inhibit the mechanistic target of rapamycin\n(mTOR) signalling, an important pathway in cancer progression. We believe that PPT1 inhibition results in changes\nin the lysosomal metabolism that result in less accumulation of antineoplastic drugs in lysosomes, which increases\nthe bioavailability of the antineoplastic agents. Taken together, these mechanisms help to explain the synergism of\nantimalarial and antineoplastic agents in cancer cells.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1389200222666211118114057","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T11:59:04Z","timestamp":1637236744000},"page":"1009-1016","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["How Antimalarials and Antineoplastic Drugs can Interact in Combination Therapies: A Perspective on the Role of PPT1 Enzyme"],"prefix":"10.2174","volume":"22","author":[{"given":"Diana","family":"Duarte","sequence":"first","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto,Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":true,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto,Portugal"}]}],"member":"965","container-title":["Current Drug Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/eurekaselect.com\/article\/download\/198076","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.eurekaselect.com\/198076\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/eurekaselect.com\/article\/download\/198076","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T09:34:30Z","timestamp":1640943270000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.eurekaselect.com\/198076\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":0,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/1389200222666211118114057","relation":{},"ISSN":["1389-2002"],"issn-type":[{"type":"print","value":"1389-2002"}],"subject":[],"published":{"date-parts":[[2021,11]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2021-06-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-15","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}