An estimated 68,000 women and men in the United States die each year from metastatic
breast and prostate cancers. Now researchers at Drexel University College of Medicine
have developed a compound directed at a target they identified that inhibits metastatic
progression by blocking tumor cells from seeding new lesions. Their discovery has been
accepted into a highly competitive drug development program at the National Cancer
Institute and will now be headed to clinical trials.
The target was initially discovered and validated in 2004 by experimental oncologist
Alessandro Fatatis, MD, PhD, professor in the Departments of Pharmacology & Physiology
and Pathology & Laboratory
Medicine. Fatatis’s initial
interest in this target stemmed
from collaboration with
Olimpia Meucci, MD, PhD,
a neuroscientist and professor
in the Department of Pharmacology
& Physiology. However,
it would be several years
before Fatatis began working
with medicinal chemist Joseph
Salvino, PhD, also a pharmacology
professor at Drexel, and
the two discovered that Salvino
could develop a compound
aimed at Fatatis’s target to
produce a new therapy to
treat cancer patients.
The compound works by
targeting circulating tumor
cells that leak into the blood,
producing new lesions, most
commonly in the skeleton,
therefore precipitating the
progression of the disease.
“Cancer cells in the blood
survive only a few hours,”
explains Fatatis. “They need
to rapidly find a new home.
What this compound does is block tumor cells from seeding again and again, and push
them toward a natural death in the blood.”
The compound specifically targets the chemokine receptor CX3CR1, which is expressed
on circulating tumor cells and implicated in metastasis to the bone.
“A significant additional benefit is that the new compounds are not toxic,” adds
Salvino. “We’re not talking about chemotherapy. We aim to develop a medication
that someone could safely take in combination with their
normal standard of care.”
The National Cancer Institute reviewed the discovery and
deemed it scientifically meritorious to accept into its highly
competitive Experimental Therapeutics Program (NExT),
which gives the scientists access to the institute’s drug
discovery, preclinical and clinical development resources
up to stage 2 clinical trials. The funding for this project
is not yet finalized, but similar programs funded through
NExT had budgets of approximately $5 million.
The trials, which should begin in the next three to five
years, will focus on advanced breast cancer patients with
evidence of metastatic disease. But both scientists believe
their discovery could have implications for other types of
cancer as well, particularly prostate cancer.
“This really is a translational scientist’s dream come true,”
said Fatatis, who, as a medical doctor in addition to a PhD,
stressed the personal significance of working on something
that could be brought from the bench to the clinic with the
potential to make a real difference for patients.
Salvino adds, “This is the true definition of scientific
collaboration. It’s not one isolated scientist in a lab. This
is the result of scientists with different areas of expertise
getting together and figuring out how to really make
This article originally appeared in the September/October 2014 issue of Pulse, the newsletter of Drexel University College of Medicine.