The Purinergic Landscape of Non-Small Cell Lung Cancer

SIMPLE SUMMARY: Lung cancer is the most prevalent cancer worldwide with poor overall survival despite many new therapeutic strategies. We discuss in this review the ability of the purinergic landscape to constitute a new potent strategy in the treatment of lung cancer. After defining lung cancer and its current treatments, we present the proteins of the purinergic landscape as well as the mechanisms leading to the production of extracellular ATP, which is at the top of the purinergic signaling chain. We also review the evidence supporting the potency of this strategy through clinical trials dedicated to the proteins of the purinergic landscape. ABSTRACT: Lung cancer is the most common cancer worldwide. Despite recent therapeutic advances, including targeted therapies and immune checkpoint inhibitors, the disease progresses in almost all advanced lung cancers and in up to 50% of early-stage cancers. The purpose of this review is to discuss whether purinergic checkpoints (CD39, CD73, P2RX7, and ADORs), which shape the immune response in the tumor microenvironment, may represent novel therapeutic targets to combat progression of non-small cell lung cancer by enhancing the antitumor immune response.