PEGylated Liposomal Teriflunomide: A Novel Approach of Targeted Breast Cancer Treatment to Advance Efficacy and Minimize Adverse Effects

Breast cancer (BC) is a life-threatening disease and the most common cancer among females, with 2.3 million cases diagnosed annually worldwide. Current treatment modalities for BC include radiation therapy, hormonal therapy, and surgical interventions, each offering therapeutic benefits but also presenting limitations and adverse effects. As a result, researchers globally are seeking novel, effective, and safer treatment options for BC patients. BC is characterized by the overexpression of human epidermal growth factor receptor 2 (HER2) and the activation of signaling pathways such as mitogen-activated protein kinases (MAPKs). Teriflunomide (TFN), an active metabolite of leflunomide, has demonstrated antiproliferative and anti-inflammatory properties. TFN inhibits de novo pyrimidine synthesis and various protein kinases, including MAPK and phosphoinositide 3-kinase (PI3K), both of which play key roles in BC pathogenesis. By targeting these signaling pathways, TFN has shown potential anticancer effects in BC. PEGylated liposomes represent a novel drug delivery system for BC treatment. This hypothesis proposes the development of teriflunomide-loaded PEGylated liposomes to enhance its therapeutic efficacy against BC. PEGylation may improve TFN’s bioavailability, tumor penetration, and anticancer activity. The synergistic interaction between the delivery system, the drug, and targeting ligands is expected to amplify TFN’s anticancer effects. This approach offers a promising, innovative solution for BC treatment and warrants further clinical investigation to validate its efficacy and safety.