Strategic Communications and Marketing News Bureau

First test of anti-cancer agent PAC-1 in human clinical trials shows promise

Portrait of Arkadiusz Dudek

Dr. Arkadiusz Dudek

CHAMPAIGN, Ill. — A phase I clinical trial of PAC-1, a drug that spurs programmed cell death in cancer cells, found only minor side effects in patients with end-stage cancers. The drug stalled the growth of tumors in the five people in the trial with neuroendocrine cancers and reduced tumor size in two of those patients. It also showed some therapeutic activity against sarcomas, scientists and clinicians report in the British Journal of Cancer.

The drug was first identified and developed as an anti-cancer agent by scientists at the University of Illinois Urbana-Champaign.

The findings from the clinical trial are noteworthy because the drug was tested in a small number of patients with advanced disease, 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. Phase I clinical trials are designed to test whether a new drug compound has worrisome side effects or toxicities in human patients, Dudek said. But scientists also can look for early evidence of therapeutic benefits. The trial enrolled cancer patients with advanced disease who had run out of other treatment options.

“We had patients with colon cancer, breast cancer, pancreatic cancer, adenocarcinoma, melanoma and others,” he said.

The clinical trial – and another testing PAC-1 against brain cancer – involves patients and clinicians at three institutions: Regions Hospital, the University of Illinois Chicago and Johns Hopkins University.

Portrait of Dr. Oana Danciu

Dr. Oana Danciu

Phase I clinical trials track side effects in patients who first are 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, said Dr. Oana Danciu, a medical oncologist and associate director for clinical research at the University of Illinois Cancer Center in Chicago, who led the clinical trial.

Researchers at the U. of I. 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 U. of I. 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 U. of I. 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,” Dudek said. “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.

If clinical trials reveal that PAC-1 is therapeutic against one or more cancer type and the drug is approved for use in those populations, it will make it less costly to test it against other cancers, the researchers said. An approved drug also can be prescribed for “off-label use” by doctors who think their patients might benefit from adding it to their cancer-treatment protocols.

It can take many years for the results of new clinical trials to be available, and longer still before a new drug like PAC-1 is approved for cancer treatment, the researchers said. 

Hergenrother and Fan are affiliates of the Carl R. Woese Institute for Genomic Biology at the U. of I. and members of the Cancer Center at Illinois.

Vanquish Oncology, the University of Illinois Cancer Center, the National Institutes of Health and the Engdahl Family Foundation supported this research.

Editor’s notes:   

To reach Dr. Arkadiusz Dudek, email adudek021@outlook.com.

To reach Dr. Oana Danciu, email ocdanciu@uic.edu.

To reach Paul Hergenrother, email hergenro@illinois.edu.

To reach Timothy Fan, email t-fan@illinois.edu.

The paper “Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies” is available online and from the U. of I. News Bureau.

DOI: 10.1038/s41416-022-02089-7

Read Next

Humanities Diptych image with book cover of "The New Internationals" and a headshot of English professor David Wright Faladé

English professor’s novel tells of love triangle in post-WWII Paris, based on his family history

CHAMPAIGN, Ill. — A new novel by University of Illinois Urbana-Champaign English professor David Wright Faladé tells the story of three people in a love triangle in post-World War II Paris. The characters in “The New Internationals” — a young French woman who has survived the Holocaust, a university student from West Africa and a […]

Life sciences Portrait of the research team posing together.

Minecraft players can now explore whole cells and their contents

CHAMPAIGN, Ill. — Scientists have translated nanoscale experimental and computational data into precise 3D representations of bacteria, yeast and human epithelial, breast and breast cancer cells in Minecraft, a video game that allows players to explore, build and manipulate structures in three dimensions. The innovation will allow researchers and students of all ages to navigate […]

Arts Photo of seven dancers onstage wearing blue tops and orange or yellow flowing skirts. The backdrop is a Persian design.

February Dance includes works experimenting with live music, technology and a ‘sneaker ballet’

CHAMPAIGN, Ill. — The dance department at the University of Illinois Urbana-Champaign will present February Dance 2025: Fast Forward this week at Krannert Center for the Performing Arts. February Dance will be one of the first performances in the newly renovated Colwell Playhouse Theatre since its reopening. The performances are Jan. 30-Feb. 1. Dance professor […]

Strategic Communications and Marketing News Bureau

507 E. Green St
MC-426
Champaign, IL 61820

Email: stratcom@illinois.edu

Phone (217) 333-5010