Anti-cancer drug shows remarkable results in human clinical trials

[Mar. 27, 2023: Staff Writer, The Brighter Side of News]

A clinical trial of PAC-1, a drug that spurs programmed cell death in cancer cells, has shown promising results in patients with end-stage cancers. The phase I trial found only minor side effects in patients, and the drug stalled the growth of tumors in five people with neuroendocrine cancers and reduced tumor size in two of those patients. The drug also showed some therapeutic activity against sarcomas, according to scientists and clinicians who published their findings in the British Journal of Cancer.

PAC-1 was first identified and developed as an anti-cancer agent by scientists at the University of Illinois Urbana-Champaign. The trial involved cancer patients with advanced disease who had run out of other treatment options.

The clinical trial, which is being conducted in conjunction with another trial testing PAC-1 against brain cancer, involves patients and clinicians at three institutions: Regions Hospital, the University of Illinois Chicago, and Johns Hopkins University.

Phase I clinical trials track side effects in patients who are first given very low doses of the compound being tested. If the drug is well-tolerated and causes no discernible toxicities over the course of a month, the dose is incrementally increased. This process can take several months before a potentially therapeutic dose is given.

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Researchers at the University of Illinois first identified PAC-1 as a potential anti-cancer compound in the early 2000s when they discovered that it could switch on a pathway that is suppressed in cancer cells. The first step of this pathway involves the conversion of procaspase-3, a protein found in most cells, into caspase-3, an enzyme that, when activated, initiates programmed cell death.

Led by chemistry professor Paul Hergenrother, the University of Illinois team also recognized that procaspase-3 occurs in greater abundance in many cancer cells relative to healthy tissues. That characteristic, along with its tendency to not be activated in cancer cells, made it a good target for anti-cancer therapies.

In animal trials involving pet dogs with spontaneously occurring lymphomas, meningiomas, and osteosarcomas, Hergenrother and Dr. Timothy Fan, a University of Illinois professor of veterinary clinical medicine, found that an early formulation of PAC-1 had anti-cancer effects. Their work in cells and in animals set the stage for the human clinical trials, which were initiated several years ago with funding from an anonymous angel investor. Hergenrother founded biotechnology company Vanquish Oncology to lead the effort.

The clinicians are currently seeking further funding to move the drug into phase II clinical trials, which would involve many more, much healthier patients with very similar cancer profiles to one another.

“Our strategy is to figure out which tumor type will be the most sensitive and pursue that,” said study clinical director Dr. Arkadiusz Dudek, an oncologist with the HealthPartners Cancer Center at Regions Hospital in St. Paul, Minnesota, and at Mayo Clinic in Rochester, Minnesota. “So we are very excited about the results in neuroendocrine tumors because there are not many drugs available for that disease.”

More results are expected soon from a phase I clinical trial of PAC-1 in patients with glioblastoma multiforme, an aggressive form of brain cancer that has only one drug available to treat it. In the new clinical trial, the team combined PAC-1 with this drug, temozolomide.

In previous studies, the researchers discovered that PAC-1 crosses the blood-brain barrier, which is essential for any brain cancer treatment. They also saw promising results of PAC-1 in combination with the drug temozolomide and radiation in pet dogs with brain cancer.

While the results of the phase I clinical trial for PAC-1 are promising, it is important to note that further research and testing are necessary before the drug can be widely used for cancer treatment. The next step is to move the drug into phase II clinical trials, which would involve a larger group of patients with similar cancer profiles. These trials will help determine the safety and efficacy of PAC-1 in a larger patient population.

In addition to the phase II clinical trials, the researchers are also exploring the use of PAC-1 in combination with other drugs to improve its therapeutic effect. For example, in the clinical trial for glioblastoma multiforme, PAC-1 was combined with temozolomide, the only drug currently approved for this type of brain cancer. The results of this trial are eagerly awaited, as they will shed more light on the potential of PAC-1 in combination with other drugs.

If the results of the phase II clinical trials are positive, PAC-1 may eventually be approved for use in cancer treatment. However, it will still take several more years before the drug is widely available to patients. In the meantime, the researchers hope that their work with PAC-1 will inspire other scientists and pharmaceutical companies to explore new ways to treat cancer.

The use of PAC-1 in the treatment of cancer is just one example of the many advances being made in cancer research. Over the past few decades, there has been a growing understanding of the complex biology of cancer, as well as new technologies and tools to study it. This has led to the development of new drugs and therapies that are more targeted and effective than traditional chemotherapy and radiation.

Despite these advances, cancer remains a leading cause of death worldwide, and there is still much work to be done to improve cancer treatment and outcomes. The researchers involved in the PAC-1 clinical trials hope that their work will contribute to this effort, and that PAC-1 will one day be part of a larger arsenal of cancer-fighting tools.

The phase I clinical trial for PAC-1 is a significant milestone in the development of this promising anti-cancer drug. The results of the trial are encouraging, showing minimal side effects and some therapeutic activity against neuroendocrine cancers and sarcomas.

While further research and testing are needed before the drug can be widely used in cancer treatment, the researchers involved in the PAC-1 clinical trials are optimistic about its potential. They hope that their work will inspire others to explore new ways to treat cancer and that one day, PAC-1 will be part of a larger arsenal of cancer-fighting tools.

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