实体肿瘤，包括乳腺癌，具有多样性，但通常以细胞增殖和代谢升高，基于复杂的肿瘤结构的扩散限制，以及异常的细胞内和细胞外离子组成，特别涉及酸碱当量为特征。癌变相关的离子通道和转运蛋白，细胞能量水平以及器官内的H+储存的表达和功能变化，进一步改变了肿瘤内部的酸碱组成，影响了癌细胞的功能，包括细胞增殖，迁移和存活。当面临肿瘤微环境中典型的细胞外H+，HCO3-和乳酸浓度明显偏离时，癌细胞比正常细胞更好地维持其细胞质的pH和HCO3-浓度。离子梯度决定了离子转运蛋白和通道的驱动力，影响膜电位。癌细胞和基质细胞也通过细胞内和细胞外受体感知异常的离子浓度，并改变癌症进展和预后。在强调乳腺癌的基础上，本文首先讨论了实体癌组织中离子组成的改变以及离子通道和转运蛋白表达和功能活性的变化。然后讨论了在酸性肿瘤微环境的影响下，离子通道，转运蛋白和细胞传感器如何塑造癌症的发展和进展，并影响癌症治疗的潜力。© 2021. Springer Nature Switzerland AG.

Solid tumors, including breast carcinomas, are heterogeneous but typically characterized by elevated cellular turnover and metabolism, diffusion limitations based on the complex tumor architecture, and abnormal intra- and extracellular ion compositions particularly as regards acid-base equivalents. Carcinogenesis-related alterations in expression and function of ion channels and transporters, cellular energy levels, and organellar H+ sequestration further modify the acid-base composition within tumors and influence cancer cell functions, including cell proliferation, migration, and survival. Cancer cells defend their cytosolic pH and HCO3- concentrations better than normal cells when challenged with the marked deviations in extracellular H+, HCO3-, and lactate concentrations typical of the tumor microenvironment. Ionic gradients determine the driving forces for ion transporters and channels and influence the membrane potential. Cancer and stromal cells also sense abnormal ion concentrations via intra- and extracellular receptors that modify cancer progression and prognosis. With emphasis on breast cancer, the current review first addresses the altered ion composition and the changes in expression and functional activity of ion channels and transporters in solid cancer tissue. It then discusses how ion channels, transporters, and cellular sensors under influence of the acidic tumor microenvironment shape cancer development and progression and affect the potential of cancer therapies.© 2021. Springer Nature Switzerland AG.