Ward Carol, Meehan James, Gray Mark E, Murray Alan F, Argyle David J, Kunkler Ian H, Langdon Simon P
Cancer Research UK Edinburgh Centre and Edinburgh Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, EH4 2XU Edinburgh, UK.
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, EH25 9RG Midlothian, UK.
Explor Target Antitumor Ther. 2020;1(2):71-100. doi: 10.37349/etat.2020.00005. Epub 2020 Apr 28.
Dysregulation of cellular pH is frequent in solid tumours and provides potential opportunities for therapeutic intervention. The acidic microenvironment within a tumour can promote migration, invasion and metastasis of cancer cells through a variety of mechanisms. Pathways associated with the control of intracellular pH that are under consideration for intervention include carbonic anhydrase IX, the monocarboxylate transporters (MCT, MCT1 and MCT4), the vacuolar-type H-ATPase proton pump, and the sodium-hydrogen exchanger 1. This review will describe progress in the development of inhibitors to these targets.
细胞pH值失调在实体瘤中很常见,为治疗干预提供了潜在机会。肿瘤内的酸性微环境可通过多种机制促进癌细胞的迁移、侵袭和转移。正在考虑进行干预的与细胞内pH值控制相关的途径包括碳酸酐酶IX、单羧酸转运体(MCT、MCT1和MCT4)、液泡型H-ATPase质子泵和钠氢交换体1。本综述将描述针对这些靶点的抑制剂的开发进展。