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In cancer cells, some compounds can induce vacuole formation, frequently producing cell death. Interestingly, vacuole\u2010induced death usually involves nonapoptotic mechanisms, such as oncosis, paraptosis and methuosis. Oncosis is characterized by rapid cellular swelling and impaired membrane transporters, affecting ion balance and causing cell rupture. In paraptosis, endoplasmic reticulum and mitochondria swell, large vacuoles form within the cells, resulting in cell lysis through specific signaling pathways. Cellular constituents are recycled and degraded during autophagy, but cells can also die from vacuoles and autophagosomes. In autophagy, damaged organelles and non\u2010functioning proteins are encapsulated in autophagosomes, which are then digested by hydrolases within the lysosome\/vacuole. Conversely, methuosis induces the formation of macropinosomes which acquire the characteristics of late endosomes, but do not fuse with lysosomes. The process of methuosis differs from apoptosis and autophagy in that it may involve specific signaling pathways. These types of nonapoptotic cell death are all triggered by the formation of vacuoles in cancer cells, and they are all potentially targets for cancer treatment. There is a need to discover and develop compounds that induce nonapoptotic cell death with vacuolization, because many types of cancer cells acquire resistance to therapies that induce apoptosis. This review will discuss compounds that induce vacuoles for various types of cells, particularly cancer cells. Our goal is to categorize and group compounds, according to their efficacy to induce vacuoles during specific types of cell death.<\/jats:p>","DOI":"10.1002\/jbt.70912","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T07:11:52Z","timestamp":1779952312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vacuolization as a Novel Approach to Cancer Therapy"],"prefix":"10.1002","volume":"40","author":[{"given":"Mariah","family":"Pasternak","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences The University of Toledo Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences The University of Toledo Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Piedra","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy University of Arkansas for Medical Sciences Little Rock Arkansas USA"},{"name":"Joint Bioinformatics Graduate Program University of Arkansas at Little Rock Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saloni","family":"Malla","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences The University of Toledo Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrabose","family":"Karthikeyan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy University of Arkansas for Medical Sciences Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1009-9169","authenticated-orcid":false,"given":"Haneen","family":"Amawi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Practice, College of Pharmacy Yarmouk University Irbid Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2008-2827","authenticated-orcid":false,"given":"Harish","family":"Rajak","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Guru Ghasidas University Bilaspur Chhattisgarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Charles R.","family":"Ashby","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy &amp; Pharmaceutical Sciences St. John's University Queens New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0337-2291","authenticated-orcid":false,"given":"R. 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