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His theories were dismissed by the medical world a decade later, but various practitioners have kept the concept alive through the publication of case reports of cancer patients treated with pancreatic proteolytic enzymes. In the last 2 decades, studies of the role of proteases in physiology have made it clear that they do more than digest food. This article reviews the history of the clinical use of pancreatic proteolytic enzymes in cancer treatment, and recent research on protease activated receptors and their role in cancer.<\/jats:p>","DOI":"10.1177\/15347354221096077","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T02:01:34Z","timestamp":1651802494000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Pancreatic Proteolytic Enzymes and Cancer: New Support for an Old Theory"],"prefix":"10.1177","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4310-8041","authenticated-orcid":false,"given":"Linda L.","family":"Isaacs","sequence":"first","affiliation":[{"name":"Private Practice, Austin, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"bibr1-15347354221096077","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)89936-0"},{"key":"bibr2-15347354221096077","volume-title":"The Enzyme Treatment of Cancer and Its Scientific Basis","author":"Beard J","year":"1911"},{"key":"bibr3-15347354221096077","doi-asserted-by":"publisher","DOI":"10.1177\/1534735408326454"},{"key":"bibr4-15347354221096077","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)42822-4"},{"key":"bibr5-15347354221096077","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.2351.140"},{"key":"bibr6-15347354221096077","first-page":"30","volume":"20","author":"Gonzalez NJ","year":"2014","journal-title":"Altern Ther Health Med"},{"key":"bibr7-15347354221096077","first-page":"1157","volume":"25","author":"Novak JF","year":"2005","journal-title":"Anticancer Res"},{"key":"bibr8-15347354221096077","volume-title":"The Enzyme Treatment for Cancer: Scientific Report on Investigations With Reference to the Treatment of Cancer","author":"Bainbridge WS","year":"1909"},{"key":"bibr9-15347354221096077","volume-title":"The Cancer Problem","author":"Bainbridge WS","year":"1914"},{"key":"bibr10-15347354221096077","first-page":"152","volume":"127","author":"May AH","year":"1928","journal-title":"Med J Rec"},{"key":"bibr11-15347354221096077","first-page":"599","volume":"28","author":"Morse FL","year":"1934","journal-title":"Weekly Bull St Louis Med Soc"},{"key":"bibr12-15347354221096077","volume-title":"Multiple Proteolytic Enzyme Therapy of Cancer","author":"Shively FL","year":"1969"},{"key":"bibr13-15347354221096077","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(82)90465-1"},{"key":"bibr14-15347354221096077","doi-asserted-by":"publisher","DOI":"10.1177\/1534735408326172"},{"key":"bibr15-15347354221096077","first-page":"73","volume":"460","author":"Isaacs LL","year":"2021","journal-title":"Townsend Lett"},{"key":"bibr16-15347354221096077","volume-title":"One Man Alone; an Investigation of Nutrition, Cancer, and William Donald Kelley","author":"Gonzalez NJ","year":"2010"},{"key":"bibr17-15347354221096077","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.24.5.274"},{"key":"bibr18-15347354221096077","first-page":"12","volume-title":"The Collection and Evaluation of Clinical Research Data Relevant to Alternative Medicine and Cancer: A Workshop Sponsored by the Office of Alternative Medicine","author":"Gonzalez NJ","year":"1996"},{"key":"bibr19-15347354221096077","volume-title":"Proof of Concept: 25 Best Cancer Cases Presented to the National Cancer Institute","author":"Gonzalez NJ","year":"2019"},{"key":"bibr20-15347354221096077","doi-asserted-by":"publisher","DOI":"10.1207\/S15327914NC330201"},{"key":"bibr21-15347354221096077","first-page":"30","volume":"14","author":"Isaacs LL","year":"2015","journal-title":"Integr Med"},{"key":"bibr22-15347354221096077","volume-title":"What Went Wrong: The Truth Behind the Clinical Trial of the Enzyme Treatment of Cancer","author":"Gonzalez NJ","year":"2012"},{"key":"bibr23-15347354221096077","unstructured":"Engel LW. 2005. 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