Shared Major Metabolic Pathways and Potential Targeted Therapies in Malignancies and Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease characterized by immune tolerance breakdown, immune cell dysfunction, and chronic inflammation. Cancer is a serious health problem and the second leading cause of mortality worldwide. Emerging evidence underscores the key role of metabolic dysregulation and the association with immunity and immune-related complications in cancer and SLE. Enhanced glycolysis and OXPHOS have been repeatedly reported in both diseases. Metabolic reprogramming is common in cancer cells and immune cells of SLE patients. In many cases, cancer cells and B cells rely on fatty acid oxidation to generate energy. Accordingly, key enzymes in those processes are also upregulated. This review summarizes current findings on major common metabolic dysregulation in cancer and SLE, highlighting the interplay of metabolic disturbances, mitochondrial dysfunction and disease pathogenesis. Furthermore, we explore the potential of targeting metabolic pathways as a therapeutic strategy to mitigate organ damage and improve outcomes in patients with SLE or cancer. We will also discuss the hurdles and prospective developments in metabolism-targeted therapy. We hope this review inspires collaborative work between cancer researchers and SLE clinicians and facilitates clinical application of cancer-metabolism-targeted drug in SLE patients.