PARP inhibitors target cellular energy metabolism: Mechanisms of action and clinical implications

Poly-ADP-ribose polymerase (PARP) is a multifunctional ribozyme that is involved in a variety of biological functions, including DNA repair, modulation of chromatin structure, RNA transcription, cell division, metabolism, mitochondrial biology, oxidative stress biology, and cell death and differentiation. PARP inhibitors (PARPi) are a new class of targeted drugs widely used in the treatment of cancer with BRCA1/2 mutations and non-malignant diseases. Although PARPi has been known to affect the energy metabolism of cells, its exact effects and mechanisms on this process have not yet been fully understood. In this review article, we aim to provide a comprehensive overview of the current understanding of PARPi's effects on various physiological processes involving cellular energy metabolism, highlighting the importance of further exploring how the human body maintains the balance of energy metabolism during PARPi therapy. We also highlight the importance of future studies on the relationship between PARPi treatment and the depletion of NAD+ levels, the activation of PARP1, or the transition between different patterns of energy metabolism, to provide more insights into the safety and efficacy of PARPi in clinical practice.