A New Generic Treatment for Multiple Types of Cancer
Researchers led by Katsunori Tanaka at the RIKEN Cluster for Pioneering
Research (CPR) in Japan and Hiromitsu Haba at the RIKEN Nishina Center
for Accelerator-Based Science (RNC) have developed a new technique that
has the potential to generically treat several kinds of cancer, with
fewer negative side effects than currently available methods. Published
on June 27 in Chemical Science, the proof-of-concept study showed that
tumors in mice grew almost three times less and survival was 100% after
just one injection of a compound that is designed to emit small amounts
of alpha radiation from the inside of cancer cells, thus killing them
but sparing healthy tissue.
The side effects of standard
chemotherapy and radiation treatment can be devastating, and the
eradication of all cancer cells is not guaranteed, especially when the
cancer has already metastasized and spread throughout the body.
Therefore, the goal of most research these days is to find a way to
specifically target cancer cells so that treatments only affect tumors.
Some targeted treatments do exist, but they cannot be applied to all
cancers. “One of the greatest advantages of our new method,” says
Tanaka, “is that is can be used to treat many kinds of cancer without
any targeting vectors, such as antibodies or peptides.”
The new
technique relies on basic chemistry and the fact that a compound called
acrolein accumulates in cancer cells. A few years ago, Tanaka’s team
used a similar technique to detect individual breast cancer cells. They
attached a fluorescent compound to a specific type of azide—an organic
molecule with a group of three nitrogen atoms (N3) at the end. When the
azide and acrolein meet inside a cancer cell, they react, and the
fluorescent compound becomes anchored to structures inside the cancer
cell. Because acrolein is almost absent from healthy cells, this
technique acted like a probe to light up cancer cells in the body.
In
the new study, rather than simply detecting cancer cells, the team
targeted those cells for destruction. The logic was fairly simple.
Instead of attaching the azide to a fluorescent compound, they attached
it to something that can kill a cell without harming surrounding cells.
The chose to work with astatine-211, a radionuclide that emits a small
amount of radiation in the form of an alpha particle as it decays.
Compared to other forms of radiation therapy, alpha particles are a
little more deadly, but they can only travel about one twentieth of a
millimeter and can be stopped by a piece of paper. In theory, when
astatine-211 is anchored to the inside a cancer cell, the emitted alpha
particles should damage the cancer cell, but not much beyond.
Once
the team figured out the best way to attach astatine-211 to the azide
probe, they were able to perform a proof-of-concept experiment to test
their theory. They implanted human lung-tumor cells into mice and tested
the treatment under three conditions: simply injecting astatine-211
into the tumor, injecting the astatine-211-azide probe into the tumor,
and injecting the astatine-211-azide probe into the bloodstream. The
found that without targeting, tumors continued to grow, and mice did not
survive. As expected, when the azide probe was used, tumors grew almost
three times less and many more mice survived — 100% when it was
injected into the tumor and 80% when injected into the blood.
“We
found that just one tumor injection with only 70 kBq of radioactivity
was extremely effective at targeting and eliminating tumor cells,” says
Tanaka. “Even when injecting the treatment compound into the
bloodstream, we were able to achieve similar results. This means we can
use this method to treat very early-stage cancer even if we don’t know
where the tumor is.” The fluorescent probe version of this technique is
already being tested in clinical trials as a way of visualizing /
diagnosing cancer at the cellular level. The next step is to find a
partner and begin clinical trials using this new method to treat cancer
in humans.
Story Source:
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Journal Reference:
Yudai Ode, Ambara R. Pradipta, Peni Ahmadi, Akihiro Ishiwata, Akiko Nakamura, Yasuko Egawa, Yuriko Kusakari, Kyohei Muguruma, Yang Wang, Xiaojie Yin, Nozomi Sato, Hiromitsu Haba, Katsunori Tanaka. Therapeutic efficacy of 211At-radiolabeled 2,6-diisopropylphenyl azide in mouse models of human lung cancer. Chemical Science, 2023; DOI: 10.1039/d3sc02513f