November 14, 2006
For the thousands of Americans diagnosed each year with oral squamous cell carcinoma, a cornerstone of their treatment is a chemotherapy drug called cisplatin. As potent as cisplatin is at killing tumor cells, a small subset often grow resistant to the drug and survive. This has left oncologists in great need of a second chemotherapy agent to kill the cisplatin-resistant cells. In the October 20 issue of the Journal of Biological Chemistry, NIDCR grantees report that they may have the solution. It’s called PS-341, which belongs to a new class of chemotherapeutic drugs that can induce apoptosis, or programmed cell death, independently of conventional cancer therapy. In a series of laboratory experiments, the scientists found PS-341 “potently” triggered apoptosis in cultured oral squamous cell carcinoma cells that were known to be resistant to cisplatin. The scientists also worked out the biochemical details, showing PS-341 does its deadly deed through a novel signaling pathway that is activated as a stress response in the endoplasmic reticulum, the cytoplasmic organelle where proteins are synthesized. “Given the fact that chemoresistance is a significant problem in cancer therapy, our results suggest that PS-341 may offer a novel alternative for treating recurrent cancer patients.”