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It summarizes PROTACs tested in ovarian cancer models, highlights candidates from other cancers relevant to ovarian cancer, and outlines delivery and pharmacodynamic strategies to improve selective therapeutic performance.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/protacs-in-ovarian-cancer-current-advancements-and-future-perspectives/336305/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/protacs-in-ovarian-cancer-current-advancements-and-future-perspectives/336305.png","ImageObject",300,407,{"name":42,"@type":43},"Ivy","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is there a need for novel therapies in ovarian cancer?","Question",{"text":63,"@type":64},"Advanced ovarian cancer commonly relapses, and subsequent treatments are often not curative. Recurrence remains a major challenge, motivating development of new therapeutic options for EOC, especially recurrent disease.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What is the central therapeutic concept behind PROTACs?",{"text":68,"@type":64},"PROTACs enable targeted protein degradation by directing proteolysis of proteins of interest. This can overcome limitations of inhibitors, such as incomplete target inhibition and resistance.",{"name":70,"@type":61,"acceptedAnswer":71},"What does the review cover regarding PROTACs for ovarian cancer?",{"text":72,"@type":64},"It summarizes PROTACs tested in ovarian cancer models and highlights PROTACs characterized in other cancer types with potential utility in ovarian cancer. 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Velázquez-Martínez 3, Amarnath Natarajan 1,2 and Adam R. Karpf 1,2, *  \nCitation: Vorderbruggen, M.; Velázquez-Martínez, C.A.; Natarajan, A.; Karpf, A.R. PROTACs in Ovarian Cancer: Current Advancements and Future Perspectives. Int. J. Mol. Sci. 2024, 25, 5067. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms25105067](10.3390/ijms25105067)  \nAcademic Editors: Giovanni Tossetta and Annalisa Inversetti  \nReceived: 4 April 2024  \nRevised: 3 May 2024  \nAccepted: 4 May 2024  \nPublished: 7 May 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA; [mvorderbruggen@unmc.edu](mvorderbruggen@unmc.edu) (M.V.); [anatarajan@unmc.edu](anatarajan@unmc.edu) (A.N.)  \n2 Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA  \n3 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada; [velazque@ualberta.ca](velazque@ualberta.ca)  \n* Correspondence: [adam.karpf@unmc.edu](adam.karpf@unmc.edu); Tel.: +402-559-6115  \nAbstract: Ovarian cancer is the deadliest gynecologic malignancy. The majority of patients diagnosed with advanced ovarian cancer will relapse, at which point additional therapies can be administered but, for the most part, these are not curative. As such, a need exists for the development of novel therapeutic options for ovarian cancer patients. Research in the field of targeted protein degradation (TPD) through the use of proteolysis-targeting chimeras (PROTACs) has significantly increased in recent years. The ability of PROTACs to target proteins of interest (POI) for degradation, overcoming limitations such as the incomplete inhibition of POI function and the development of resistance seen with other inhibitors, is of particular interest in cancer research, including ovarian cancer research. This review provides a synopsis of PROTACs tested in ovarian cancer models and highlights PROTACs characterized in other types of cancers with potential high utility in ovarian cancer. Finally, we discuss methods that will help to enable the selective delivery of PROTACs to ovarian cancer and improve the pharmacodynamic properties of these agents.  \nKeywords: ovarian cancer; PROTAC; targeted protein degradation; high-grade serous ovarian cancer  \n1. Ovarian Cancer  \nOvarian cancer is estimated to be the fifth leading cause of cancer-related deaths among U.S. women [1] . Ovarian cancer is broadly subdivided into three types: germ cell, sex-cord stromal, and epithelial (EOC), with EOC being the most common, accounting for approximately 90% of cases [2] . EOC is further subdivided into mucinous, endometrioid, clear cell, low-grade serous (LGSC), and high-grade serous (HGSOC), with HGSOC accounting for 70–80% of EOC cases, making it the most common subtype of ovarian cancer [2] .  \nTreatment of EOC consists of debulking surgery coupled with chemotherapy [2] . When possible, patients receive primary debulking surgery to remove as much of the tumor as is feasible, followed by adjuvant platinum-and taxane-based chemotherapy [3] . In cases of highly advanced disease or difficult-to-resect tumors, interval debulking surgery is used, where patients first receive primary chemotherapy to reduce the disease burden followed by debulking surgery [3] . Approximately 70% of patients treated with platinumand taxane-based chemotherapy respond favorably to treatment and achieve remission [4] . However, one of the major cha","cbCaiqrCY3SgweG9","https://ap.wps.com/l/cbCaiqrCY3SgweG9","pdf",1167172,15,"English","# Ovarian Cancer\n## Treatment overview\n# Ubiquitin–Proteasome System\n## Ubiquitin conjugation and E3 ligases\n## Polyubiquitination and proteasome degradation","[{\"question\":\"Why is there a need for novel therapies in ovarian cancer?\",\"answer\":\"Advanced ovarian cancer commonly relapses, and subsequent treatments are often not curative. Recurrence remains a major challenge, motivating development of new therapeutic options for EOC, especially recurrent disease.\"},{\"question\":\"What is the central therapeutic concept behind PROTACs?\",\"answer\":\"PROTACs enable targeted protein degradation by directing proteolysis of proteins of interest. This can overcome limitations of inhibitors, such as incomplete target inhibition and resistance.\"},{\"question\":\"What does the review cover regarding PROTACs for ovarian cancer?\",\"answer\":\"It summarizes PROTACs tested in ovarian cancer models and highlights PROTACs characterized in other cancer types with potential utility in ovarian cancer. It also discusses methods to support selective delivery and improve pharmacodynamic properties.\"}]","PROTACs in Ovarian Cancer - Current Advancements and Future Perspectives | PDF",1790014477,38]