Cisplatin is a chemotherapeutic alkylating agent that causes intrastand crosslinks that is more difficult to repair than regular DNA. Cisplatin diffuses into the cell either through the membrane or through metal transporter like CTR1. In the cytosol, the low concentration of chloride relative to the extracellular space causes hydrolysis of cisplatin into its aquo complex which goes into the nucleus and binds to DNA bases. It preferentially binds to guanine but can also bind to adenine bases. It's used for treated testicular cancer, ovarian cancer and other solid tumors and it targets all parts of the cell cycle (cell-cycle non specific). Most patients will eventually develop resistance to cisplatin though as cancer cells will decrease uptake or pump it out of the cell through exocytotic vesicles. Patients will has have increased production of cellular thiols like GSH which inactivates the aquated cisplatin by forming a complex with it. Cisplatin is administered intravenously usually to the site of the tumor. Cisplatin can cause nephrotoxicity due to ROS generation as well as nausea and vomiting.

Cisplatin Pathway References