What Factors Lead to Cisplatin Resistance?

Cisplatin is a drug administered to people with certain forms of cancer as part of a chemotherapy treatment plan organized and provided by medical professionals. The human body can develop cisplatin resistance because of factors including targeted cells becoming immune to the ingredients of the drug, and different molecules within a cell rejecting cisplatin before it has the opportunity to work effectively. Cisplatin attempts to damage the DNA within cancerous cells; the body naturally attempts to repair damaged DNA with proteins, so some cells repair the damage caused by cisplatin, reducing the effectiveness of the drug.

Resistance to the drug is one of the major reasons for the discontinuation of cisplatin during a course of chemotherapy. The colorless fluid is usually administered directly into a vein in the hand, arm, or collarbone in long sessions of up to eight hours over a period of months. The cancer cells, including those that cause testicular, lung, and bladder cancers, are targeted by cisplatin in an attempt to kill the cells and halt the spread of the disease through the body.

One factor allowing cisplatin resistance to develop is the ability of a cell to alter its characteristics and form a defense that does not allow the drug to penetrate and act within it. Reasons for the failure of the drug to penetrate cancerous cells, a process known as decreased intracellular accumulation, are not known by researchers. One theory suggests the cancerous cell is required to actively help pass cisplatin through its exterior and, after long-term use, can stop this assistance, leaving the drug to move around the bloodstream without being absorbed.

To work effectively, cisplatin works directly on the DNA of a cancer cell to destroy it from within. There are more molecules within a cell than just DNA that can interact with and expel the drug to increase the chance of cisplatin resistance occurring. Detoxifying molecules within the cells of the body help to maintain good health and expel pollutants. The detoxifier metallothionein expels heavy metals from inside cells and is thought to attract cisplatin. After being attracted to the molecule, cisplatin is expelled from the cancerous cell before it has the opportunity to damage the DNA.

Some proteins are thought to aid the DNA within a cell in repairing itself following exposure to chemotherapy drugs. Cisplatin resistance can occur when those proteins are present within a cell targeted by the medication. Levels of proteins, such as the XPE-BF nuclear protein, often rise following the administering of chemotherapy drugs for a long period of time, increasing the likelihood of cisplatin resistance.