New cancer treatment targets acrolein in cancer cells

A team of researchers led by Katsunori Tanaka at the RIKEN Cluster for Pioneering Research (CPR) in Japan, along with Hiromitsu Haba at the RIKEN Nishina Center for Accelerator-Based Science (RNC), has made significant progress in developing a novel technique for treating various types of cancer. The study, published on June 27 in Chemical Science, demonstrated promising results in mice, showing that tumors grew significantly less and the survival rate was 100% after a single injection of a compound designed to emit small amounts of alpha radiation from within cancer cells, effectively killing them while sparing healthy tissue.

Current treatments such as chemotherapy and radiation often come with severe side effects, and they do not guarantee complete eradication of cancer cells, particularly in cases where the cancer has metastasized throughout the body. Consequently, researchers are focusing on finding methods that specifically target cancer cells, minimizing the impact on healthy tissue. While some targeted treatments exist, they are not applicable to all types of cancer.

The new technique developed by Tanaka’s team offers several advantages, as it can potentially treat multiple forms of cancer without the need for targeting vectors like antibodies or peptides. The method relies on fundamental chemistry principles and exploits the fact that acrolein, a compound that accumulates in cancer cells, can be utilized. In a previous study, Tanaka’s team used a similar technique to detect individual breast cancer cells by attaching a fluorescent compound to a specific type of azide—a type of organic molecule ending in three nitrogen atoms (N3).

In this new study, the researchers went beyond detection and targeted the cancer cells for destruction. They attached the azide to a substance capable of killing a cell without harming surrounding cells. They selected astatine-211, a radionuclide that emits a small amount of radiation in the form of an alpha particle as it undergoes decay.

Compared to other radiation therapies, alpha particles are highly lethal but have limited range, traveling only about one-twentieth of a millimeter and easily stopped by a piece of paper. The concept was straightforward: by anchoring astatine-211 to the inside of a cancer cell using the azide probe, the emitted alpha particles would damage the cancer cell without affecting neighboring cells.

After determining the optimal method for attaching astatine-211 to the azide probe, the researchers conducted a proof-of-concept experiment to validate their hypothesis. They implanted human lung tumor cells into mice and tested the treatment under three conditions: injecting astatine-211 directly into the tumor, injecting the astatine-211-azide probe into the tumor, and injecting the astatine-211-azide probe into the bloodstream.

The results showed that without targeting, tumors continued to grow, leading to poor survival rates. However, when the azide probe was used, tumors grew significantly less, and a higher number of mice survived—100% when injected into the tumor and 80% when injected into the bloodstream.

Tanaka highlighted the efficacy of the treatment, stating that a single tumor injection with a mere 70 kBq of radioactivity was remarkably effective in targeting and eliminating tumor cells. Additionally, even when the treatment compound was injected into the bloodstream, similar results were achieved. This indicates that the method could be used to treat early-stage cancer, even when the exact location of the tumor is unknown.

The fluorescent probe version of this technique is already being tested in clinical trials for visualizing and diagnosing cancer at the cellular level. The next step is to find a partner and commence clinical trials using this new method for cancer treatment in humans.

Source: RIKEN

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