Cisplatin, a commonly used chemotherapeutic, has always had a severe side effect. Although a potent chemotherapy drug, cisplatin has been known to cause severe kidney damage, leading to renal failure in many patients that take the drug. Although previously, doctors simply measured creatinine levels to gauge whether the nephrotoxic effects were taking place and tried to counteract them when they were found, now there may be a solution to this side effect. The Journal of Clinical Investigation recently published an article in which they articulate that using another drug in concert with cisplatin can help reduce renal damage. Researchers found that by inhibiting PKC-δ, the damages to the kidney were significantly reduced.
Data shows that Src activates PKC-δ when in the presence of cisplatin in kidney cells. Activated PKC-δ translocated into the nucleus is important for cytotoxic and apoptotic function. In the presence of cisplatin, there are excess amounts of activated PKC-δ, inducing massive amounts of cytotoxic and apoptotic events. Rottlerin, a PKC-δ inhibitor, was used in experiments to see whether stopping the damage to kidney cells reduced the efficacy of cisplatin. In Figure A, tumor mass decreases almost identically in cisplatin and cisplatin + rottlerin treatments. However, levels of creatinine in the cisplatin + rottlerin treatment are significantly lower than the levels in the cisplatin treatment as shown by Figure D.
Since creatinine is measured to determine whether kidneys are failing, it shows that when cisplatin is given with rottlerin, there is significantly less damage done to the kidneys. Creatinine levels are an easy way of measuring renal failure because the kidney filters creatinine out of the blood at a relatively constant rate. If levels rise past a certain point, it is obvious that there is an issue in the kidneys.
Cisplatin is used to treat many different kinds of cancers, including sarcomas, carcinomas and lymphomas. Due to its usefulness, maximizing the use of it while reducing the severe side effects is a large step to making the drug a better treatment. If potent chemotherapies have very undesirable side effects, they are less likely to be used. However, simply decreasing the rate of renal failure in patients that take this chemotherapeutic is not enough. Other side effects of cisplatin are neurotoxicity, damage of nerve cells, and ototoxicity, hearing loss. Hearing loss caused by cisplatin cannot be restored afterwards and currently there are no treatments to prevent this severe effect from occurring. Although scientists could work to find ways of helping a chemotherapy drug like cisplatin have less adverse effects, is it really worth it? Will people be willing to put more drugs into their body not just to get rid of their cancer but to help prevent side effects as well? At what point is it too much?
Although it does take many years to develop new effective treatments, I believe that currently there is not much of a choice. Hopefully as time progresses, targeted chemotherapies with few side effects will come into use more. Because who really knows what all these extra drugs can do in people’s bodies until after they have been taken?
