{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/117518"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/117518","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Identifying the basis for anticancer synergy with PAC-1, with applications to meningioma","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-12-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-12-01","abstract_has_math":false,"creators":["Tonogai, Emily J."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Hergenrother, Paul J","Mitchell, Douglas A","Chan, Jefferson","Mehta, Angad P"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-12","date_published":"2022-12","updated_at":"2026-07-22T22:24:56Z","subjects":["cancer","meningioma","uveal melanoma","PAC-1","caspase","procaspase","small molecule","comparative oncology","canine"],"languages":["en","eng"],"rights":["Copyright 2022 Emily Tonogai"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/117518","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Hergenrother, Paul J","Mitchell, Douglas A","Chan, Jefferson","Mehta, Angad P"]},{"key":"dc:creator","label":"Author","values":["Tonogai, Emily J."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-12","2022-08-17"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["cancer","meningioma","uveal melanoma","PAC-1","caspase","procaspase","small molecule","comparative oncology","canine"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2022 Emily Tonogai"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/117518"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-12-01","The student, Emily Tonogai, accepted the attached license on 2022-08-02 at 12:58.","The student, Emily Tonogai, submitted this Dissertation for approval on 2022-08-02 at 13:05.","This Dissertation was approved for publication on 2022-08-17 at 09:28.","DSpace SAF Submission Ingestion Package generated from Vireo submission #18441 on 2023-04-12 at 11:34:08","The procaspase-3/-7 activator, PAC-1, selectively activates apoptosis in cancerous cells by leveraging the overexpression of caspase-3 in a broad spectrum of cancer types. This unique mechanism is thought to contribute to the ability of PAC-1 to synergize with a variety of different therapeutics, which has been demonstrated in numerous literature reports. Herein, previously reported combinations with PAC-1 in different cancer types will be reviewed and recent research on new combinations will be described. In particular, focus will be placed on PAC-1 in combination with temozolomide (TMZ) and hydroxyurea (HU) in high-grade meningioma, a rare form of brain cancer with no FDA-approved therapies. PAC-1 + TMZ was found to have activity in canine patients with meningioma. Additionally, recent work has demonstrated the synergy of PAC-1 in combination with the NTRK/ROS1/ALK inhibitor entrectinib, in metastatic uveal melanoma which has led to a clinical trial. Further efforts to evaluate the synergy of this combination and understand its mechanism will also be described. While PAC-1 has been reported to synergize with a broad spectrum of therapeutics, the underlying mechanism of this synergy has not yet been investigated. The diversity of caspase substrates cleaved during apoptosis may contribute to the ability of PAC-1 to synergize with such a wide variety of different therapies. To begin investigating the source of PAC-1’s broad synergy, the effect of PAC-1 on proteins involved in DNA repair pathways are investigated as many of these have been reported as caspase substrates. Understanding the proteins affected by PAC-1- induced caspase activity may inform our understanding of published PAC-1 combinations as well as aid in the design of novel combinations."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Identifying the basis for anticancer synergy with PAC-1, with applications to meningioma"]}]}],"canonical_facts":{"dc:contributor":["Hergenrother, Paul J","Mitchell, Douglas A","Chan, Jefferson","Mehta, Angad P"],"dc:creator":["Tonogai, Emily J."],"dc:date":["2022-12","2022-08-17"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-12-01","The student, Emily Tonogai, accepted the attached license on 2022-08-02 at 12:58.","The student, Emily Tonogai, submitted this Dissertation for approval on 2022-08-02 at 13:05.","This Dissertation was approved for publication on 2022-08-17 at 09:28.","DSpace SAF Submission Ingestion Package generated from Vireo submission #18441 on 2023-04-12 at 11:34:08","The procaspase-3/-7 activator, PAC-1, selectively activates apoptosis in cancerous cells by leveraging the overexpression of caspase-3 in a broad spectrum of cancer types. This unique mechanism is thought to contribute to the ability of PAC-1 to synergize with a variety of different therapeutics, which has been demonstrated in numerous literature reports. Herein, previously reported combinations with PAC-1 in different cancer types will be reviewed and recent research on new combinations will be described. In particular, focus will be placed on PAC-1 in combination with temozolomide (TMZ) and hydroxyurea (HU) in high-grade meningioma, a rare form of brain cancer with no FDA-approved therapies. PAC-1 + TMZ was found to have activity in canine patients with meningioma. Additionally, recent work has demonstrated the synergy of PAC-1 in combination with the NTRK/ROS1/ALK inhibitor entrectinib, in metastatic uveal melanoma which has led to a clinical trial. Further efforts to evaluate the synergy of this combination and understand its mechanism will also be described. While PAC-1 has been reported to synergize with a broad spectrum of therapeutics, the underlying mechanism of this synergy has not yet been investigated. The diversity of caspase substrates cleaved during apoptosis may contribute to the ability of PAC-1 to synergize with such a wide variety of different therapies. To begin investigating the source of PAC-1’s broad synergy, the effect of PAC-1 on proteins involved in DNA repair pathways are investigated as many of these have been reported as caspase substrates. Understanding the proteins affected by PAC-1- induced caspase activity may inform our understanding of published PAC-1 combinations as well as aid in the design of novel combinations."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/117518"],"dc:language":["en","eng"],"dc:rights":["Copyright 2022 Emily Tonogai"],"dc:subject":["cancer","meningioma","uveal melanoma","PAC-1","caspase","procaspase","small molecule","comparative oncology","canine"],"dc:title":["Identifying the basis for anticancer synergy with PAC-1, with applications to meningioma"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:56Z"}