Ovarian cancer and the heart - pathophysiology, chemotherapy-induced cardiotoxicity, and new therapeutic strategies

Sep 23, 2026

Uploaded by Margaret

Ovarian Cancer (OC) is the most lethal gynecologic malignancy, driven by many genetic mutations that enable uncontrolled cellular growth and replication. Non-coding RNAs, including miRNAs and lncRNAs, regulate OC through roles in tumor initiation, progression, metastasis, immune evasion, and chemoresistance, supporting their value as diagnostic markers and therapeutic targets. Standard OC care uses cytoreductive surgery and chemotherapy, yet agents like doxorubicin cause cardiotoxicity from acute to chronic outcomes, including heart failure and death. Strategies to improve response and reduce cardiac harm include liposomal doxorubicin, radiotherapy, immunotherapy, and combined cardiac-protective drugs. PDE5 inhibitors may also lessen treatment-related cardiotoxicity and induce apoptosis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Introduction

Mechanisms of ovarian cancer

Ovarian cancer and treatment-related cardiotoxicity

Chemotherapy-induced cardiotoxicity and doxorubicin

Therapeutic strategies to reduce cardiotoxicity

Nair et al. Journal of Ovarian Research (2025) 18:72 Journal of Ovarian Research [https://doi.org/10.1186/s13048-025-01636-z](https://doi.org/10.1186/s13048-025-01636-z) REVIEW Open Access Ovarian cancer and the heart: pathophysiology, chemotherapy-induced cardiotoxicity, and new therapeutic strategies Megha Nair 1, Arun Samidurai 1, Anindita Das 1, Sham S. Kakar2 and Rakesh C. Kukreja 1* Abstract Ovarian Cancer (OC) is recognized as the most lethal gynecologic malignancy, characterized by numerous genetic mutations that trigger uncontrolled cellular growth and replication. Emerging evidence suggests that non-coding RNAs including miRNAs and lncRNAs significantly influence OC through their multiple roles including tumor initiation, progression, metastasis, immune evasion, and chemoresistance, making them promising diagnostic markers and therapeutic targets. The primary approach to treating OC typically involves cytoreductive surgery followed by chemotherapy. However, the chemotherapeutic agents, particularly the anthracyclines such asdoxorubicin (DOX), are known for their cardiotoxic effects, which can range from acute to chronic, potentially leading to heart failure and death. To enhance the overall treatment response and to minimize cardiotoxicity, alternative strategies have been explored. These include the use of liposomal doxorubicin (DOXIL) as a substitute for DOX, various radiotherapies, immunotherapies, and the co-administration of angiotensin-converting enzyme inhibitors and/or beta-blockers. Phosphodiesterase-5 inhibitors (PDE5i) have also demonstrated efficacy in reducing cardiotoxicity linked to cancer treatments and in promoting apoptosis in cancer cells across multiple cancer types. Although there is no current clinical trial directly examining the impact of PDE5i on reducing cardiotoxicity in OC, however emerging therapies such as Withaferin A, PARP inhibitors, and nanoparticle combination therapy show promise. Additional research is essential to develop treatments that are both effective against OC and less harmful to the heart. Keywords Ovarian cancer, PDE5 inhibitors, Cardiotoxicity, Chemotherapy, Doxorubicin *Correspondence: Rakesh C. Kukreja [rakesh.kukreja@vcuhealth.org](rakesh.kukreja@vcuhealth.org) 1Department of Internal Medicine, Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA 2Department of Physiology, University of Louisville, Louisville, KY, USA © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/. Nair et al. Journal of Ovarian Research (2025) 18:72 Introduction Globally, Ovarian Cancer (OC) is the seventh most common cancer in women and the eighth leading cause of cancer death with a five-year survival rate below 45%[1]. It is the most lethal among the gynecologic cancers, and the number of cases is increasing with life expectancy [1]. More than 22,000 new cases are diagnosed annually i

FAQs

Why is ovarian cancer considered particularly lethal?

Ovarian cancer is described as the most lethal gynecologic malignancy because it is associated with numerous genetic mutations that drive uncontrolled cellular growth and replication.

How does chemotherapy, especially doxorubicin, affect the heart?

Anthracyclines such as doxorubicin are known for cardiotoxic effects that can range from acute to chronic and may progress to heart failure and death.

What alternative or additional strategies are discussed to reduce cardiotoxicity?

The document discusses substituting doxorubicin with liposomal doxorubicin, exploring radiotherapies and immunotherapies, using co-administration of ACE inhibitors and/or beta-blockers, and considering PDE5 inhibitors as potential cardioprotective and pro-apoptotic options.

Sep 23, 2026

Uploaded by Margaret