Department of Medical Sciences, University of Ferrara, Italy.
Department of Medical Sciences, University of Ferrara, Italy.
Pharmacol Ther. 2024 Oct;262:108700. doi: 10.1016/j.pharmthera.2024.108700. Epub 2024 Aug 5.
Innovation of cancer therapy has received a dramatic acceleration over the last fifteen years thanks to the introduction of the novel immune checkpoint inhibitors (ICI). On the other hand, the conspicuous scientific knowledge accumulated in purinergic signaling since the early seventies is finally being transferred to the clinic. Several Phase I/II clinical trials are currently underway to investigate the effect of drugs interfering with purinergic signaling as stand-alone or combination therapy in cancer. This is supporting the novel concept of "purinergic immune checkpoint" (PIC) in cancer therapy. In the present review we will address a) the basic pharmacology and cell biology of the purinergic system; b) principles of its pathophysiology in human diseases; c) implications for cell death, cell proliferation and cancer; d) novel molecular tools to investigate nucleotide homeostasis in the extracellular environment; e) recent developments in the pharmacology of P1, P2 receptors and related ecto-enzymes; f) P1 and P2 ligands as novel diagnostic tools; g) current issues in PIC-based anti-cancer therapy. This review will provide an appraisal of the current status of purinergic signaling in cancer and will help identify future avenues of development.
过去十五年，由于新型免疫检查点抑制剂（ICI）的引入，癌症治疗的创新得到了显著加速。另一方面，自 70 年代初以来，嘌呤能信号在科学知识方面的显著积累终于被应用于临床。目前正在进行几项 I/II 期临床试验，以研究干扰嘌呤能信号的药物作为单一或联合疗法在癌症中的作用。这支持了癌症治疗中“嘌呤能免疫检查点”（PIC）的新概念。在本综述中，我们将讨论：a）嘌呤能系统的基本药理学和细胞生物学；b）其在人类疾病中的病理生理学原理；c）对细胞死亡、细胞增殖和癌症的影响；d）研究细胞外环境核苷酸动态平衡的新型分子工具；e）P1、P2 受体及相关外切酶药理学的最新进展；f）P1 和 P2 配体作为新型诊断工具；g）基于 PIC 的抗癌治疗的当前问题。本综述将评估嘌呤能信号在癌症中的当前状况，并有助于确定未来的发展方向。
