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Advancing cancer therapies by innovatively tackling cancer in pets
Cancer is a top killer that impacts the lives of both humans and animals. The typical cancer drug discovery process is often long and the costs are high. In the standard model, cancer is induced in lab mice and rats, and these lab animals are then treated to test a drug’s efficacy. Unfortunately, this model is not widely successful and leads to tremendous inefficiencies: over 90% of cancer drugs that are effective in mice show disappointing results in human trials and hence do not become drugs. But what if we could efficiently advance the best cancer therapeutics by successfully treating pets with naturally-occurring cancers? Dr. Paul J. Hergenrother, Professor of Chemistry at University of Illinois, Urbana-Champaign (U of I) develops new cancer drugs in a novel way, and evaluates candidate drugs in pets—specifically dogs and cats—who have naturally-occurring cancer. He is advancing effective cancer therapies that benefit both animal and human patients.
Many dogs and cats suffer from cancer, and are typically euthanized because there are no viable treatment options. Dr. Hergenrother offers experimental therapeutics developed in his lab to tackle common cancers in pets—lymphoma, osteosarcoma, brain cancers, among others—which share close genetic similarities to the human diseases. By evaluating candidate drugs in a veterinary cancer patients, Dr. Hergenrother’s lab is able to advance the most promising cancer drugs to humans. Dr. Hergenrother and his interdisciplinary team includes collaborators and students specializing in chemical biology, organic chemistry, cell biology, pharmacology, and veterinary oncology. They closely collaborate with Professor Tim Fan, a U of I veterinary oncologist, as well as specialists in cancer biology and biostatistics. Together, they have already treated more than 50 pet dogs suffering from cancer with a new drug therapy they discovered. After receiving positive data—tumor regression in late-stage canine cancer patients with metastatic disease—through their canine clinical trials, Dr. Hergenrother and his team were able to apply this to human patients. That compound is currently being evaluated in more than a dozen human cancer patients in an ongoing phase 1 clinical trial at University of Illinois Clinical Cancer Center and Johns Hopkins Hospital.
Current research includes:
Discovering Novel Methods to Tackle Cancer - Dr. Hergenrother and his team have developed a novel strategy to construct thousands of drug candidates, and aim to exploit specific defects in a cancer cell. By hitting therapeutic targets, they develop high-value and complex molecules that instruct cancer cells to die. Once they test these novel compounds in cultured cancer cells, they identify those that work most effectively. From there, they test the compounds in mice, moving the most promising to pet dogs and cats with naturally-occurring cancers. Once they successfully treat these pets, they are able to intelligently prioritize which compounds will work in humans and advance the therapies in human clinical trials.
Treating Childhood Cancer - Dr. Hergenrother and his team are evaluating compounds they discovered to treat dogs with bone cancer (osteosarcoma) and brain cancers. Detailed genetic analyses have shown that these canine cancers are very similar to their human counterparts. Osteosarcoma often leads to lung metastasis; about 80 percent of dogs suffering from bone cancer die from lung metastases. Dr. Hergenrother and his team are able to obtain quantitative data by taking x-rays to measure tumors and apply treatments. In multiple cases, they’ve shrunk metastatic lesions and have helped these pet dogs with cancer. Their compounds combine very well with existing standard of care drugs to improve effectiveness. They aim to now translate these findings to pediatric cancer patients.
Treating Adult Cancers - Dr. Hergenrother and his team are using their novel compounds to treat pet dogs with brain cancer. They’ve treated canine patients suffering from meningioma (an intracranial tumor), and glioblastoma, which are very difficult to treat in humans. Because canine and human brain cancers are similar, the most effective compounds will advance to treat humans with brain cancer. They will soon be initiating a phase 1 clinical trial with human glioblastoma patients.
To learn more, visit Dr. Hergenrother’s website at http://www.hergenrothergroup.com.
Bio
Dr. Paul J. Hergenrother has always wanted to tackle large unsolved biomedical problems. After receiving his B.S. in chemistry from the University of Notre Dame in 1994, he obtained his Ph.D. at the University of Texas at Austin in 1999. It was there that he received the American Chemical Society graduate student fellowship and the Roche Award for Excellence in Organic Chemistry.
After pursuing an American Cancer Society postdoctoral fellowship at Harvard University, Dr. Hergenrother joined the faculty at University of Illinois (U of I) in 2001. With the unveiling of the human genome and in-depth molecular details on cancer research, efforts to treat cancer became more promising. Though still a very challenging problem, rapidly expanding molecular details about cancer make this a ripe time for attacking this disease that affects so many. Dr. Hergenrother’s novel research in identifying effective anticancer compounds is motivated by the opportunity to solve big problems, where the solutions can have a positive and major impact on human health.
In the early stages of his research, Dr. Hergenrother began a collaboration with a veterinarian oncologist from U of I’s prominent veterinary medicine school, Professor Tim Fan. After creating potent compounds, they started treating canine patients in 2007. He currently has one compound treating patients in a human clinical trial, and aims to greatly expand the efforts of his novel research to treat more canine and human patients suffering from cancer.
When he’s not in the lab, Dr. Hergenrother enjoys playing basketball and spending time with his wife and three children.
In the News
Publications
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Awards
Innovation Transfer Award, 2016
University of Illinois and Champaign County
University Scholar, 2014-2017
American Cancer Society Research Scholar, 2006-2010
Eli Lilly Award in Biological Chemistry, 2008
Camille Dreyfus Teacher-Scholar
David Robertson Award for Excellence in Medicinal Chemistry, 2006
I. C. Gunsalus Scholar, UIUC, 2006-2007
Patents
U. S. Patent No: 9,233,960: “Compounds and Anti-Tumor NQO1 Substrates"
U. S. Patent No: 9,233,960: “Compounds and Anti-Tumor NQO1 Substrates.” Inventors: Hergenrother, P.J.; Boothman, D. A.; Bair, J. S.; Palchaudhuri, R.; Parkinson, E. I. Issued January 12, 2016.
U. S. Patent No: 9,102,661: “Design, Synthesis and Evaluation of Procaspase Activating Compounds as Personalized Anti-Cancer Drugs.”
U. S. Patent No: 9,102,661: “Design, Synthesis and Evaluation of Procaspase Activating Compounds as Personalized Anti-Cancer Drugs.” Inventors: Hergenrother, P. J.; Peterson, Q. P.; Hsu, D. C.; West, D. C.; Fan, T. M; Novotny, C. H. Issued August 11, 2015.
U.S. Patent No: 8,778,945: "Design, Synthesis and Evaluation of Procaspase Activating Compounds as Personalized Anti-Cancer Drugs."
U.S. Patent No: 8,778,945: "Design, Synthesis and Evaluation of Procaspase Activating Compounds as Personalized Anti-Cancer Drugs." Inventors: Hergenrother, P. J.; Peterson, Q. P.; Hsu, D. C.; West, D. C.; Fan, T. M; Novotny, C. H. Issued July 15, 2014.
U.S. Patent No: 8,754,084: "Therapeutic Methods and Agents for Treating Myotonic Dystrophy."
U.S. Patent No: 8,754,084: "Therapeutic Methods and Agents for Treating Myotonic Dystrophy." Inventors: Zimmerman, S.C.; Hergenrother, P. J.; Wong, C.-H.; Peh, J. Issued June 17, 2014.
U.S. Patent No: 8,592,584: “Compositions and Methods Including Cell Death Inducers and Procaspase Activation.”
U.S. Patent No: 8,592,584: “Compositions and Methods Including Cell Death Inducers and Procaspase Activation.” Inventors: Hergenrother, P. J.; Putt, K. S.; Peterson, Q. P.; Fako, V. Issued November 26, 2013.
U.S. Patent No 7,709,465: “Phosphorous-Containing Compounds Including Triphenylmethylphosphonate Esters for the Treatment of Melanoma and Other Cancers.”
U.S. Patent No 7,709,465: “Phosphorous-Containing Compounds Including Triphenylmethylphosphonate Esters for the Treatment of Melanoma and Other Cancers.” Inventors: Hergenrother, P. J.; Nesterenko, V.; Putt, K. S.; Palchaudhuri, R. Issued May 4, 2010.
U.S. Patent No 7,632,972: “Compounds and Methods for Treatment of Cancer and Modulation of Programmed Cell Death for Melanoma and Other Cancer Cells.”
U.S. Patent No 7,632,972: “Compounds and Methods for Treatment of Cancer and Modulation of Programmed Cell Death for Melanoma and Other Cancer Cells.” Inventors: Hergenrother, P. J.; Nesterenko, V.; Putt, K. S.; Allen, B. J.; Leslie, B.; Dothager, R. Issued Dec. 15, 2009.