Tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment due to their effectiveness in cancer cell killing. However, an off-target of this agent limits its success. Cardiotoxicity-associated TKIs have… Click to show full abstract
Tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment due to their effectiveness in cancer cell killing. However, an off-target of this agent limits its success. Cardiotoxicity-associated TKIs have been widely reported. Tyrosine kinase is involved in many regulatory processes in a cell, and it is involved in cancer formation. Recent evidence suggests the role of tyrosine kinase in cardiovascular calcification, specifically, the calcification of heart vessels and valves. Herein, we summarized the accumulating evidence of the crucial role of receptor tyrosine kinase (RTK) in cardiovascular calcification and provided the potential clinical implication of TKIs-related ectopic calcification. We found that RTKs, depending on the ligand and tissue, can induce or suppress cardiovascular calcification. Therefore, RTKs may have varying effects on ectopic calcification. Additionally, in the context of cardiovascular calcification, TKIs do not always relate to an unfavored outcome—they might offer benefits in some cases. Graphical Abstract Summary of evidence of TK's involvement in cardiovascular calcification. The TKs can either induce or suppress calcification depend on the TK subtype, ligand, and tissue. The increase of vessel calcification can be induced by the activation of EGFR, PDGFR, FGFR, DDR, c-MET, TIE2, and ROR (left upper panel), whereas the suppression on vessel calcification can be due to the activation of FGFR, IGFR, TRK, and AXL (left lower panel). In the valve of heart tissue, the activation of FGFR, TRK, TIE2, and VEGFR can increase heart's valve calcification (right upper panel). In contrast, the EGFR, IGFR and FGFR activation suppress calcification of heart's valve (right lower panel). This dual role of TK in cardiovascular calcification might explain the various effect of TKI in cardiovascular calcification.
               
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