[GRG] NewAbs: Cancer Drug for Lymphomas and Osteosarcomas Works in Dogs (PAC-1)

To Members and Friends of the Los Angeles Gerontology
Research Group:Cancer Rx
for Lymphomas and Osteosarcomas… — Steve Coles”Cancer Drug Shows Promise in
Pet Dogs” Wednesday, July 17, 2013; (Drug Discovery and
Development) — Thanks to a new $ 2 million investment, a drug that
spurs cancer cells to self-destruct while sparing healthy cells is on the
road to human clinical trials. The compound, known as PAC-1, has so far
proven safe and has promising anti-cancer effects in cell culture, in
mouse models of cancer, and in pet dogs with spontaneously occurring
lymphomas and osteosarcomas.If PAC-1
(Pack One) makes it through the U.S. Food and Drug Administration’s
Investigational New Drug review, the first human (Phase-1) clinical trial
of the drug will begin in mid-2014. The investor, who wishes to remain
anonymous, has an option to invest another $ 2 million to take the drug
into human trials. The clinical work will be conducted at the University
of Illinois Cancer Center in Chicago.“The trial
is going to be geared toward brain cancer patients,” said U. of I.
Chemistry Professor Paul Hergenrother, who discovered PAC-1’s anti-cancer
capabilities in 2006 and has been refining and testing it ever since.
“One of the unusual features of this drug is that it does get into the
brain, which most cancer drugs do not. So we want to embrace that and try
to address the unmet clinical need of brain cancer.”The
researchers noted that the compound is still in the early stages of
development, and must pass toxicological tests in two species as well as
other pharmacology toxicity testing before it can be tried in human
subjects.The new
investment is the outgrowth of years of testing and development of PAC-1
and derivative compounds in dogs with naturally occurring cancers, said
Illinois Professor of Veterinary Clinical Medicine Tim Fan, who
coordinated clinical trials of the drug in canine patients at the U. of
I. Veterinary Teaching Hospital.“We know
that mice will always be used as a traditional model for cancer
research,” Fan said. “But conventional preclinical models use mice with
induced cancers, which fail to faithfully recapitulate the development of
natural cancers. This means that novel therapeutics that may be effective
in mice might fail in patients that develop cancer spontaneously, as
observed in both dogs and people.”The
researchers emphasized that the dogs used in the testing of PAC-1 were
pets from the community with spontaneously occurring cancers, not
laboratory animals with induced cancers.“In
addition to paving the way for the human trial, we have helped many
veterinary patients that would not have otherwise received treatments for
their cancer,” Fan said.
“PAC-1 targets a cellular enzyme, ProCaspase-3, that when
activated spurs a series of reactions inside the cell that cause it to
self-destruct,” Hergenrother said. Procaspase-3 has long been an
attractive target for cancer therapy, in part because cancers often
interfere with normal cell death, and in part because many tumors –
including those of the breast, colon, liver, and lung, along with
lymphoma and
melanoma –
contain high levels of Procaspase-3.“The
target, Procaspase-3 activation, and the extensive amount of in vitro
and animal data that Dr. Hergenrother and Dr. Fan had generated are
what attracted me to this project,” said Ted Tarasow, the CEO of
Vanquish Oncology, a drug development startup company founded by
Hergenrother and Tarasow in 2011.
“Procaspase-3 activation has long been recognized as a high potential
target for oncology therapeutics, but largely has been met with
frustration in terms of finding compounds that could actually influence
its activity in vivo,” Tarasow said. “And so the compounds that professor
Hergenrother developed and that Vanquish is pursuing are likely to be the
first procaspase-3-activating agents to make it to the clinic despite a
lot of interest and investment in this target over the years.”
Vanquish Oncology “has exclusively licensed the technology from the
University of Illinois and is focused on moving PAC-1 into the clinic,”
Tarasow said. “As with any investigational agent, determining the true
safety and efficacy profile of PAC-1 will take several years of human
clinical trials.”PAC-1 has
other desirable attributes, said Arkadiusz Dudek, a Physician and
Professor of Hematology and Oncology at the U. of I. at Chicago.“What is
interesting about Hergenrother’s discovery is that it has a unique
ability to penetrate to brain tumors,” said Dudek, who will design and
supervise the first PAC-1 clinical trial in humans at the U. of I. Cancer
Center. “This is an area of interest for us. If successful, it will make
a huge impact on survival, quality of life and disease control in
patients with primary or metastatic brain tumors.”