The results of the study, conducted by researchers at the University of Illinois, appear this month in the journal Cancer Research.
The new compound targets a cellular enzyme, procaspase-3, that when activated spurs a cascade of reactions that kill the cell, said chemistry professor Paul Hergenrother, who co-led the study with Tim Fan, a professor of veterinary clinical medicine.
Procaspase-3 offers an attractive target for cancer therapy, in part because cancers often interfere with normal cell death, and in part because many tumors – including those found in breast cancer, colon cancer, lung cancer, lymphoma, melanoma and liver cancer – contain high levels of procaspase-3.
“In my lab, we try to think of novel targets and novel approaches to cancer and other diseases,” Hergenrother said. “We think about the pathways that lead to those diseases, and we try to intervene at spots where others have not.”
The new compound is a modified version of a drug the researchers previously tested in mice and one dog.
The original compound, called PAC-1, was found to cause neurological excitation (neurotoxicity) even at low doses, the researchers said. Fan and his colleagues hypothesized that PAC-1, which works in part by grabbing zinc away from other molecules, was crossing the blood/brain barrier and latching onto zinc in the brain.
To prevent the compound from passing into the brain, Hergenrother’s laboratory made a derivative of PAC-1 with an added chemical group, called a sulfonamide. Tests in pet dogs with spontaneously occurring lymphoma showed that the new compound, S-PAC-1, stabilized or reduced the size of tumors in a majority of the animals, without neurotoxicity. Other side effects were mild, and recent adjustments to the treatment protocol have minimized or eliminated them, the researchers report.
If S-PAC-1 proves to be effective and safe as a lymphoma treatment and is approved by the FDA for use in dogs and/or humans (a process that could take years, the researchers emphasized), it will likely be added to the arsenal of drugs already used to combat lymphoma in both dogs and humans. It could be used in combination with other drugs as a first treatment option or serve as a second line of defense if the cancer returns.
Cancer drug combinations must be carefully tailored to avoid “overlapping toxicities,” Fan said, so a drug that effectively treats lymphoma with minimal side effects is very desirable.
The study in pet dogs is also unusual, Fan said, as most studies look at effects in mice and then, if a compound is promising and appears safe, it is tested in clinical trials in humans. The six dogs used in this study were veterinary patients that had spontaneously developed lymphoma, he said.
The similarities between human and canine lymphoma also add to the desirability of this approach, Hergenrother said.
“If you look at the genetic signatures of canine lymphoma and human lymphoma, they’re very, very similar and their response to therapy is very, very similar,” he said. “So there’s lots of reasons to be optimistic about a compound that has some effect in the canines, that it could have a similar effect in humans.”
This study was supported by funding from the National Cancer Institute at the National Institutes of Health. A new $525,000 grant from the NCI will support a clinical trial of S-PAC-1 in companion animal dogs. More information about the upcoming trial is available online: http://vetmed.illinois.edu/vth/MedServices/SmallAnimal/CancerCareClinic/CancerCareClinic.html
Diana Yates | University of Illinois
Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie
Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
20.09.2017 | Life Sciences
20.09.2017 | Power and Electrical Engineering
20.09.2017 | Physics and Astronomy