TRPM2-mediated Ca2+ signaling as a potential therapeutic target in cancer treatment: an updated review of its role in survival and proliferation of cancer cells

The transient receptor potential melastatin subfamily member 2 (TRPM2), a thermo and reactive oxygen species (ROS) sensitive Ca²⁺-permeable cation channel has a vital role in surviving the cell as well as defending the adaptability of various cell groups during and after oxidative stress. It shows higher expression in several cancers involving breast, pancreatic, prostate, melanoma, leukemia, and neuroblastoma, indicating it raises the survivability of cancerous cells. In various cancers including gastric cancers, and neuroblastoma, TRPM2 is known to conserve viability, and several underlying mechanisms of action have been proposed. Transcription factors are thought to activate TRPM2 channels, which is essential for cell proliferation and survival. In normal physiological conditions with an optimal expression of TRPM2, mitochondrial ROS is produced in optimal amounts while regulation of antioxidant expression is carried on. Depletion of TRPM2 overexpression or activity has been shown to improve ischemia-reperfusion injury in organ levels, reduce tumor growth and/or viability of various malignant cancers like breast, gastric, pancreatic, prostate, head and neck cancers, melanoma, neuroblastoma, T-cell and acute myelogenous leukemia. This updated and comprehensive review also analyzes the mechanisms by which TRPM2-mediated Ca²⁺ signaling can regulate the growth and survival of different types of cancer cells. Based on the discussion of the available data, it can be concluded that TRPM2 may be a unique therapeutic target in the treatment of several types of cancer. Video Abstract.