New generic cancer treatment spares healthy tissue

Scientists at Japan’s RIKEN research institution have developed a new way to generically treat several kinds of cancer, with fewer negative side effects than other methods. As explained in the journal Chemical Science, the team utilised 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.

Given that the side effects of standard chemotherapy and radiation treatment can be devastating, the goal of much research these days is to find a way to specifically target cancer cells so that treatments only affect tumours. Unlike other targeted treatments, which cannot be applied to all cancers, the RIKEN method 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, Katsunori Tanaka’s team at the RIKEN Cluster for Pioneering Research 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 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, instead of attaching the azide to a fluorescent compound, the team attached it to something that can kill a cell without harming surrounding cells. They 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 millimetre 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.

In a proof-of-concept experiment, the team implanted human lung-tumour cells into mice and tested the treatment under three conditions: simply injecting astatine-211 into the tumour, injecting the astatine-211–azide probe into the tumour and injecting the astatine-211–azide probe into the bloodstream. They found that without targeting, tumours continued to grow and mice did not survive. When the azide probe was used, tumours grew almost three times less and many more mice survived — 100% when it was injected into the tumour and 80% when injected into the blood.

“We found that just one tumour injection with only 70 kBq of radioactivity was extremely effective at targeting and eliminating tumour cells,” Tanaka said. “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 tumour is.”

The fluorescent probe version of this technique is already being tested in clinical trials as a way of visualising cancer at the cellular level. The next step is to find a partner and begin clinical trials to treat cancer in humans.

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