New advances in cancer treatment involve using on-site synthesis of anticancer drugs

An international research group at the RIKEN Cluster for Pioneering Research (CPR) in Wako, Saitama, Japan has found success in treating cancer in mice using metal catalysts that gather anticancer drugs together inside the body, according to new research.

According to the study, published in the journal, Nature Communications, scientists focused on therapeutic in vivo synthetic chemistry being used to make anticancer substances by vein injection. Researchers anticipate this technique will have a significant impact on cancer treatment because it avoids indiscriminate tissue damage.

Katsunori Tanaka, chief scientist at RIKEN CPR, who led the new study, has developed a method for activating non-toxic compounds using transition-metal catalysis inside the body. When the catalyst is injected into an organism, it usually has no effect because it is destroyed by antioxidants such as glutathione. By placing the transition-metal catalysts inside special pockets within a protein, Tanaka and his colleagues have been able to avoid this problem and stabilize the catalytic function in vivo, ensuring that the chemical reaction can proceed efficiently in the body, according to the research.

For this technique to work, the catalyst needs to selectively find its way to the cancer. As in their previous studies, the team targeted the catalyst to the cancer by attaching chains of cancer-binding sugar molecules to the surface of the carrier protein. Using these techniques, Tanaka’s group succeeded in inhibiting cancer growth and metastasis, as well as reducing the side effects. The new study is a proof of concept in which cancer in mice was treated by assembling anticancer drugs inside the body near the cancer cells.

“In the past, we used similar methods to attach anticancer drugs to tumors,” said Tanaka, “But here, we were able to avoid putting any toxic drugs into the body at all.”

Noting that the basic skeleton of most anticancer drugs contains a benzene ring, the researchers started by making benzene rings inside the body using transition-metal catalysts. Using a transition metal-catalyzed complex designed for selective delivery to cancerous tissues, they succeeded in efficiently creating the benzene-rings needed by cancer drugs in the vicinity of cancer cells. By using non-toxic substances, and only joining them together to form active anticancer drugs at the tumor site, they saw a 1000-times increase in the cancer-inhibiting activity of the drugs. Simply administering the ingredients needed for the drug, along with the transition-metal catalyst, through a vein, cancer growth was inhibited without side effects such as weight loss.

“Many patients with cancer are dying because of the side effects of treatment,” said Tanaka. “We believe our technology, which attacks cancer cells highly effectively without side effects, will be able to save lives. “The method will also allow us to reconsider using compounds that have not been used before because they were too toxic when delivered to the whole body. Now they can be synthesized at the tumor site without affecting healthy tissue. We believe this is a paradigm shift for pharmaceuticals and drug discovery.”