Paul J. Hergenrother, Ph.D.
Most cells have a limited life span and eventually die of old age triggered by an internal death signal. But cancer cells don’t respond to this death signal. Sometimes, the activation of the death signal is blocked. V Foundation funded scientist Dr. Paul Hergenrother’s and his team at University of Illinois at Urbana-Champaign (UIUC) identified a molecule called PAC-1 which activates the death signal. They found that by combining PAC-1 with existing chemotherapeutics makes the drugs more effective. Breast cancer is a type of cancer that seems to be particularly susceptible to this PAC-1 – chemo drug combination.
Dr. Hergenrother was awarded a Designated Grant in 2013 and used this grant to identify several particularly effective PAC-1 drug combinations. They decided to focus in on the PAC 1-doxorubin combination for further study.
Interestingly, pet dogs have become man’s best friend in yet another way. In a research approach sometimes called Canine Comparative Oncology, treatment of cancers in pet dogs is providing valuable insights into new drug development for human patients. Dr. Hergenrother’s lab group has investigated the PAC-1- Doxorubicin combination in pet dogs with naturally-occurring cancer with metastases to the lung, similar to those observed in human breast cancer.
In an exciting recent result, a pet dog that was treated with PAC-1 + Doxorubicin had a measurable decrease in its lung metastases upon two cycles of this therapy. This is extremely exciting as metastatic cancer in canines is very difficult to treat. These outcomes with pet dogs have opened the possibility of using this combination in a new phase 1 clinical trial in human cancer patients with metastatic breast cancer. These discussions are on-going, and may result in a new trial in 2017.
Many new anti-cancer compounds appear promising when initial studies are done in mice, but then fail when these results cannot be replicated when tested in humans. The mice model is often not the ideal model. New collaborative research efforts between veterinarians as they treat their canine patients may provide much better model data for human cancers and lead to quicker identification of the most promising molecules. Because companion animals like dogs are often afflicted with cancers that are similar at the genetic level to human cancers, respond to therapeutics similarly to humans, are exposed to the same toxins and have metastatic disease like humans, drug candidates effective in these pets with cancer may be more likely to also be efficacious against the human disease.
Dr. Hergenrother, in collaboration with veterinarian Dr. Tim Fan, a Professor in the department of Veterinary Clinical Medicine at UIUC, has evaluated PAC-1/drug combinations in over 50 pet dogs with lymphoma, metastatic osteosarcoma and meningioma. The promising results of their work resulted in submission of a new Investigational New Drug (IND) application to the FDA, and founding of a start-up company called Vanquish Oncology. The FDA approved the IND, and the Phase I clinical trial of PAC-1 in human cancer patients is on-going at the University of Illinois Cancer Center in Chicago and at the Sidney Kimmel Cancer Center at Johns Hopkins. Please see this link on clinicaltrials.gov for more information.