Breast Cancer: Targets and Therapy (Sep 2018)
Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer
Abstract
Yesenia L Franco,* Tanaya R Vaidya,* Sihem Ait-Oudhia Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL, USA *These authors contributed equally to this work Abstract: Breast cancer (BC) is a highly prevalent disease, accounting for the second highest number of cancer-related mortalities worldwide. The anthracycline doxorubicin (DOX), isolated from Streptomyces peucetius var. caesius, is a potent chemotherapeutic drug that is successfully used to treat various forms of liquid and solid tumors and is currently approved to treat BC. DOX exerts its effects by intercalation into DNA and inhibition of topoisomerases I and II, causing damage to DNA and the formation of reactive oxygen species (ROS), resulting in the activation of caspases, which ultimately leads to apoptosis. Unfortunately, DOX also can cause cardiotoxicity, with patients only allowed a cumulative lifetime dose of 550 mg/m2. Efforts to decrease cardiotoxicity and to increase the blood circulation time of DOX led to the US Food and Drug Administration (FDA) approval of a PEGylated liposomal formulation (L-DOX), Doxil® (known internationally as Caelyx®). Both exhibit better cardiovascular safety profiles; however, they are not currently FDA approved for the treatment of metastatic BC. Here, we provide detailed insights into the mechanism of action of L-DOX and its most common side effects and highlight results of its use in clinical trials for the treatment of BC as single agent and in combination with other commonly used chemotherapeutics. Keywords: doxil, caelyx, breast cancer, anti-tumor activity, cardiotoxicity
