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 "We found that a surprising number of non-oncology drugs are able to
kill cancer cell lines in the lab," said Dr. Steven Corsello of
Dana-Farber Cancer Institute and the Broad Institute of MIT and
Harvard University, who led the research.
Dr. Bruce Bloom of Cambridge, Massachusetts-based Healx, a company
that uses artificial intelligence to discover drugs for rare
diseases, told Reuters Health by email the new drug targets and
mechanisms of action identified by the researchers could be valuable
both for new treatment approaches and for repurposing older drugs.
Published this week in Nature Cancer, the work is the largest yet to
use the Broad Institute's Drug Repurposing Hub (http://bit.ly/36rJTS2),
a collection of samples of more than 6,000 drugs and compounds that
are either approved by the U.S. Food and Drug Administration or have
gone through early-stage clinical trials proving they are safe in
people.
The researchers tested the drugs on more than 550 different cancer
cell lines.
Earlier efforts at this kind of discovery have been painstaking
because researchers had to grow cell lines one at a time and test
each drug individually. This time, they used DNA barcodes -
introducing unique snippets of DNA with a virus to label the cell
lines. This technique allowed them to pool the cell lines,
shortening screening time.
"We tested 4,518 compounds in this experiment in total," Corsello,
founder of the Drug Repurposing Hub, said in a telephone interview.
"We found 49 non-oncology drugs that were able to selectively kill
cancer cell lines - killing some but not other cancers, which is an
ideal property."
The researchers selected four of these drugs to undergo more testing
to better understand how they attacked and killed cancer cells.
These included a treatment for diabetes, a drug for inflammation, a
treatment for alcohol abuse and one for treating arthritis pain in
dogs.
Most of the drugs they tested attacked cancer in novel ways.
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The drug tepoxalin, for example, which was originally developed for
use in people but later approved for treating osteoarthritis in
dogs, worked by attacking a target called MDR1 that's expressed on
the surface of cells and protects them from chemotherapy.
Corsello said cancer patients who develop resistance to chemotherapy
often have high levels of this protein.
Antabuse, a drug approved to treat alcohol dependence, showed
activity in cancers that lack a portion of chromosome 16, which
commonly occurs in some breast cancers.
Other drugs showing anti-cancer properties included a compound
originally developed to treat diabetes called vanadium, and
levonorgestrel, a hormone used in contraceptives.
Corsello's team plans to conduct animal studies on some of the drugs
to see which have the best chances of success in a clinical trial,
and they plan to test even more cancer drugs for anti-cancer
properties.
He sees the approach being useful in two ways. In limited cases in
which the drug is promising enough, the treatment could be quickly
brought into clinical trials in cancer patients. But Corsello
believes the more likely use is to identify new and unexpected
molecular targets that could lead to cancer treatments.
Bloom, who was not involved with the study, said the paper
"highlights the struggle to balance transparency and sharing of
discoveries, with heavily patent-dependent commercialization
requirements for therapies to make it to market."
He said while the data support the repurposing of non-oncology drugs
to oncology and could lead to even more discoveries, the disclosure
of specific drug names and targets might make it harder for
companies to protect future repurposed and new treatment
discoveries.
SOURCE: https://go.nature.com/2NXzQ0K Nature Cancer, online January
20, 2020.
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