{"id":{"repo_id":"nus","oai_identifier":"oai:scholarbank.nus.edu.sg:10635/216716"},"canonical_url":"https://search.dev.ndltd.org/etd/nus/oai:scholarbank.nus.edu.sg:10635/216716","repository":{"repo_id":"nus","name":"National University of Singapore","base_url":"https://scholarbank.nus.edu.sg/oai/request"},"display":{"title":"DEGRADATION OF XIAP AS A NOVEL TREATMENT STRATEGY IN HIGH-RISK NEUROBLASTOMA","abstract":"The potential of XIAP antagonism as a treatment strategy for neuroblastoma has not been investigated despite neuroblastoma being an embryonal cancer with a developmental biology requiring XIAP. Here, we showed that the targeting of XIAP, and not other IAP members such as c-IAPs, was necessary to trigger apoptotic death in neuroblastoma, and that this was effected specifically via degradation and not inhibition. ARTS mimetic A4, a newly-identified XIAP-specific antagonist, was found to be highly potent towards neuroblastoma cells, and is tolerable and non-toxic towards non-cancerous normal cells, in comparison to pan-IAP antagonists. A4 catalyzed rapid degradation of XIAP through a ubiquitin-proteasomal pathway, worked synergistically with standard-of-care cytotoxic agents and prolonged the overall survival of high-risk MYCN-amplified neuroblastoma patient-derived xenografts. Collectively, this presents the degradation of XIAP mediated by ARTS mimetics as a potential therapeutic strategy for treatment of neuroblastoma, specifically aggressive high-risk MYCN-amplified disease which intrinsically overexpresses XIAP.","abstract_html":"The potential of XIAP antagonism as a treatment strategy for neuroblastoma has not been investigated despite neuroblastoma being an embryonal cancer with a developmental biology requiring XIAP. Here, we showed that the targeting of XIAP, and not other IAP members such as c-IAPs, was necessary to trigger apoptotic death in neuroblastoma, and that this was effected specifically via degradation and not inhibition. ARTS mimetic A4, a newly-identified XIAP-specific antagonist, was found to be highly potent towards neuroblastoma cells, and is tolerable and non-toxic towards non-cancerous normal cells, in comparison to pan-IAP antagonists. A4 catalyzed rapid degradation of XIAP through a ubiquitin-proteasomal pathway, worked synergistically with standard-of-care cytotoxic agents and prolonged the overall survival of high-risk MYCN-amplified neuroblastoma patient-derived xenografts. Collectively, this presents the degradation of XIAP mediated by ARTS mimetics as a potential therapeutic strategy for treatment of neuroblastoma, specifically aggressive high-risk MYCN-amplified disease which intrinsically overexpresses XIAP.","abstract_has_math":false,"creators":["CHOO ZHANG'E"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-08-11","date_published":"2021-08-11","updated_at":"2026-07-24T03:31:38Z","subjects":["Neuroblastoma, XIAP, apoptosis, treatment, degradation, ARTS mimetic"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["CHOO ZHANG'E"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2021-08-11"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://scholarbank.nus.edu.sg/handle/10635/216716"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Neuroblastoma, XIAP, apoptosis, treatment, degradation, ARTS mimetic"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://scholarbank.nus.edu.sg/bitstreams/00fdfafe-16a7-4459-a1a6-636109c976c2/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The potential of XIAP antagonism as a treatment strategy for neuroblastoma has not been investigated despite neuroblastoma being an embryonal cancer with a developmental biology requiring XIAP. Here, we showed that the targeting of XIAP, and not other IAP members such as c-IAPs, was necessary to trigger apoptotic death in neuroblastoma, and that this was effected specifically via degradation and not inhibition. ARTS mimetic A4, a newly-identified XIAP-specific antagonist, was found to be highly potent towards neuroblastoma cells, and is tolerable and non-toxic towards non-cancerous normal cells, in comparison to pan-IAP antagonists. A4 catalyzed rapid degradation of XIAP through a ubiquitin-proteasomal pathway, worked synergistically with standard-of-care cytotoxic agents and prolonged the overall survival of high-risk MYCN-amplified neuroblastoma patient-derived xenografts. Collectively, this presents the degradation of XIAP mediated by ARTS mimetics as a potential therapeutic strategy for treatment of neuroblastoma, specifically aggressive high-risk MYCN-amplified disease which intrinsically overexpresses XIAP."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["bd0201bf6174aa170b91c9851e766ccf","e34ef909e961e6d51bece5154e428e77"]},{"key":"dc:title","label":"Title","values":["DEGRADATION OF XIAP AS A NOVEL TREATMENT STRATEGY IN HIGH-RISK NEUROBLASTOMA"]}]}],"canonical_facts":{"dc:creator":["CHOO ZHANG'E"],"dc:date.issued":["2021-08-11"],"dc:description.abstract":["The potential of XIAP antagonism as a treatment strategy for neuroblastoma has not been investigated despite neuroblastoma being an embryonal cancer with a developmental biology requiring XIAP. Here, we showed that the targeting of XIAP, and not other IAP members such as c-IAPs, was necessary to trigger apoptotic death in neuroblastoma, and that this was effected specifically via degradation and not inhibition. ARTS mimetic A4, a newly-identified XIAP-specific antagonist, was found to be highly potent towards neuroblastoma cells, and is tolerable and non-toxic towards non-cancerous normal cells, in comparison to pan-IAP antagonists. A4 catalyzed rapid degradation of XIAP through a ubiquitin-proteasomal pathway, worked synergistically with standard-of-care cytotoxic agents and prolonged the overall survival of high-risk MYCN-amplified neuroblastoma patient-derived xenografts. Collectively, this presents the degradation of XIAP mediated by ARTS mimetics as a potential therapeutic strategy for treatment of neuroblastoma, specifically aggressive high-risk MYCN-amplified disease which intrinsically overexpresses XIAP."],"dc:format.checksum.md5":["bd0201bf6174aa170b91c9851e766ccf","e34ef909e961e6d51bece5154e428e77"],"dc:identifier.uri":["https://scholarbank.nus.edu.sg/bitstreams/00fdfafe-16a7-4459-a1a6-636109c976c2/download"],"dc:relation.isreferencedby":["https://scholarbank.nus.edu.sg/handle/10635/216716"],"dc:subject":["Neuroblastoma, XIAP, apoptosis, treatment, degradation, ARTS mimetic"],"dc:title":["DEGRADATION OF XIAP AS A NOVEL TREATMENT STRATEGY IN HIGH-RISK NEUROBLASTOMA"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T03:31:38Z"}