Advancements and Obstacles of PARP Inhibitors in Gastric Cancer

SIMPLE SUMMARY: Gastric cancer (GC) is a highly aggressive malignancy affecting the digestive system and characterized by notable variations in its nature. Although survival rates have observed some enhancements, the prognosis remains grim, and mortality rates remain high. There is an immediate demand for innovative treatment strategies. Recent investigations have identified frequent mutations in genes responsible for repairing DNA damage in GC patients, highlighting the potential of PARP inhibitors (PARPi) as a promising therapeutic option. This article offers a comprehensive examination of the progress and hurdles in the development of PARPi for treating GC. ABSTRACT: Gastric cancer (GC) is a common and aggressive cancer of the digestive system, exhibiting high aggressiveness and significant heterogeneity. Despite advancements in improving survival rates over the past few decades, GC continues to carry a worrisome prognosis and notable mortality. As a result, there is an urgent need for novel therapeutic approaches to address GC. Recent targeted sequencing studies have revealed frequent mutations in DNA damage repair (DDR) pathway genes in many GC patients. These mutations lead to an increased reliance on poly (adenosine diphosphate-ribose) polymerase (PARP) for DNA repair, making PARP inhibitors (PARPi) a promising treatment option for GC. This article presents a comprehensive overview of the rationale and development of PARPi, highlighting its progress and challenges in both preclinical and clinical research for treating GC.