Ovarian cancer and the heart: pathophysiology, chemotherapy-induced cardiotoxicity, and new therapeutic strategies
Megha Nair, Arun Samidurai, Anindita Das, Sham S. Kakar, Rakesh C. Kukreja
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 as doxorubicin (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.