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Standard care relies on debulking surgery and platinum-based therapies, yet innate and acquired resistance drives relapse and renders the disease incurable. The review synthesizes knowledge of the genetic landscape and molecular pathways across OC subtypes, emphasizing how convergent alterations shape progression and treatment resistance. 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Oncogenic Pathways and Targeted Therapies in Ovarian Cancer. Biomolecules 2024, 14, 585. [https://](https://)[ ](https://)[doi.org/10.3390/biom14050585](doi.org/10.3390/biom14050585)  \nAcademic Editor: Jorge Joven  \nReceived: 4 April 2024  \nRevised: 6 May 2024  \nAccepted: 11 May 2024  \nPublished: 15 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 Cancer Program, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; [carolina.lliberos@monash.edu](carolina.lliberos@monash.edu)  \n2 Neil Beauglehall Department of Medical Oncology Research, Cabrini Health, Malvern, VIC 3144, Australia  \n* Correspondence: [gary.richardson@cabrini.com.au](gary.richardson@cabrini.com.au) (G.R.); [antonella.papa@monash.edu](antonella.papa@monash.edu) (A.P.); Tel.: +613-9508-3446 (G.R.); +613-9902-9330 (A.P.)  \nAbstract: Epithelial ovarian cancer (EOC) is one of the most aggressive forms of gynaecological malignancies. Survival rates for women diagnosed with OC remain poor as most patients are diagnosed with advanced disease. Debulking surgery and platinum-based therapies are the current mainstay for OC treatment. However, and despite achieving initial remission, a significant portion of patients will relapse because of innate and acquired resistance, at which point the disease is considered incurable. In view of this, novel detection strategies and therapeutic approaches are needed to improve outcomes and survival of OC patients. In this review, we summarize our current knowledge of the genetic landscape and molecular pathways underpinning OC and its many subtypes. By examining therapeutic strategies explored in preclinical and clinical settings, we highlight the importance of decoding how single and convergent genetic alterations co-exist and drive OC progression and resistance to current treatments. We also propose that core signalling pathways such as the PI3K and MAPK pathways play critical roles in the origin of diverse OC subtypes and can become new targets in combination with known DNA damage repair pathways for the development of tailored and more effective anti-cancer treatments.  \nKeywords: ovarian cancer; signalling pathways; targeted therapies; PI3K; MAPK  \n1. Introduction  \nIn 2022 there were ~325,000 new reported cases of ovarian cancer (OC) and ~207,000 OC deaths worldwide [1] . By 2045, the global incidence of OC is expected to increase by 47%, with a projected rise in deaths of 58%[2] . While OC is the 11th most common cancer among women (2.5% of cancers), it is the 5th leading cause of cancer-related death, with a relative five-year survival rate of ~50.8%[3] .  \nOnly 15% of OC cases are identified during the early and localized stage of the disease, which is generally associated with better outcomes and a 5-year survival rate of~90%[4] . However, a large portion of OC, ~60%, are diagnosed when the cancer has already metastasized to distant sites, a condition that significantly reduces the 5-year survival rate to ~30%[4] . These numbers highlight the urgent need to identify new OC biomarkers for earlier detection and more rapid intervention.  \nCurrent screening methods for OC detection are based on pelvic examination, including transvaginal ultrasound and evaluation of the cancer antigen 125 (CA-125), a peptide produced by OC cells together with mesothelial cells from multiple tissues such as the endometrium [4,5] . Once diagnosed, ","cbCaitfzUUtuGVMI","https://ap.wps.com/l/cbCaitfzUUtuGVMI","pdf",2078175,24,"English","# Abstract\n# 1. Introduction\n## Epidemiology and stage at diagnosis\n## Screening and first-line treatment\n# 2. Ovarian Cancer: Pathological Classification, Subtyping and Associated Mutations","[{\"question\":\"Why do many ovarian cancer patients relapse after initial remission?\",\"answer\":\"Relapse occurs because of innate and acquired resistance to current platinum-based therapies, after which the disease is considered incurable.\"},{\"question\":\"What current strategies are used for ovarian cancer treatment and detection?\",\"answer\":\"Detection relies on pelvic examination with transvaginal ultrasound and CA-125 evaluation. Treatment typically uses surgery followed by platinum-based chemotherapy.\"},{\"question\":\"Which signaling pathways are proposed as important targets for tailored therapies?\",\"answer\":\"The review highlights core signaling pathways, especially PI3K and MAPK, and proposes combining them with known DNA damage repair pathway targets to improve treatment effectiveness.\"}]","Oncogenic Pathways and Targeted Therapies in Ovarian Cancer - Review | PDF",1790041030]