Researchers at Fox Chase Cancer Center Identify a Large Number of New Cancer-Fighting Molecules

• A research team led by Alexei Tulin, PhD, associate professor at Fox Chase Cancer Center, has identified a new group of chemicals that are effective at eliminating cancer in living tissue. This discovery prompted a fruitful collaboration with several Fox Chase oncologists, in which new treatments were found to be effective in a laboratory setting against drug-resistant PARP-1 tumors. These treatments had minimal toxicity and fewer side effects than conventional treatments. The new group of PARP-1 inhibitors was effective at eliminating breast, kidney, and prostate cancer. The study appears online in the journal EBioMedicine.

  Tulin and his colleagues developed a new method for identifying highly potent PARP-1 inhibitors and presented the largest known collection of structurally diverse inhibitors. Their new strategy for testing the molecules involves blindly screening a small molecule library for PARP-1 inhibitors by targeting the highly specific route of PARP-1 activation. Using this screening strategy, the researchers were able to identify new inhibitors that block PARP-1 activity in cancer cells more effectively and with less toxicity.

  “Our inhibitors are very specific and not toxic or for normal tissues” Tulin said. “The main advantage of these inhibitors is the absence of toxicity and off-target effects.”

  With more than 100 active clinical studies testing the efficacy and specificity of many PARP-1 inhibitors for cancer treatment, identifying more effective and less toxic inhibitors has become a vital area of cancer research. Tulin’s team has shown that the new inhibitors are effective against several different cancers. Their research makes a compelling case for testing these newly discovered inhibitors on a variety of cancers in human clinical trials.