Treatment for bone cancer unexpectedly makes tumors less painful

Cancer that spreads to the bones can be fatal and is also often painful. Now, the drug appears to solve both problems by disrupting the interplay between nerves and tumors, suggesting that this approach could provide a more convenient form of cancer treatment.

“This highlights a new, exciting paradigm where a single cancer treatment can improve mortality and quality of life simultaneously,” he says William Hwang at Harvard University, who was not involved in the new research.

Between 65 and 80 percent people with breast or prostate cancer that has spread to distant places in the body will end up with cancer in their bones. As these skeletal tumors grow, they tend to stimulate nearby pain-sensing nerves.

Radiotherapy, in which X-rays are fired at tumors, and chemotherapy, which uses strong drugs to target rapidly dividing cells, are commonly used to shrink such bone growths. But the pain often persists because the remaining cancer cells continue to interact with the nerves. What’s more, conventional therapy often damages healthy tissue, leading to long-term use of painkillers like opioids that carry the risk of addiction, he says Jiajia Xiang at Zhejiang University in China.

Now Xiang and his colleagues have developed a “nanotherapy” made of tiny, greasy capsules containing DNA encoding the protein gasdermin B, which kills cells by poking holes in them. The drug was designed to produce gasdermin B only in cancer cells and not healthy ones, based on the idea that cancer cells can be distinguished from other cells because they have higher levels of certain molecules called reactive oxygen species. The capsules also contain a chemical called OPSA, which boosts the body’s natural anti-cancer immune response.

To test their drug, the researchers injected each of several mice with one leg of breast cancer cells. Once the cancer cells had grown into bone tumors, each mouse received either the complete nanotherapy, a simpler form of nanotherapy that contained OPSA but not the gasdermin B gene, or a control saline solution. All treatments were injected into the tail every other day for five days.

Two weeks later, the tumors in the complete nanotherapy group were on average 94 percent smaller than in the control group, compared to about 50 percent in the simpler nanotherapy group. After another few weeks, all of the mice that received the complete nanotherapy were alive, while only 60 percent of the mice in the simpler nanotherapy group survived and only 20 percent of the control mice. As expected, the therapy directly killed the tumor cells and triggered an anti-tumor immune response, Xiang says.

But the team also noticed that mice receiving one form of nanotherapy used their cancerous limbs significantly more than those in the control group, with the full nanotherapy group seeing greater benefits. This suggests that nanotherapy may reduce the pain associated with bone tumors. When the researchers analyzed tumor samples taken from the mice, they were surprised to find that both nanotherapies reduced the density of nerve cells, or neurons, in the cancer cells.

Nanotherapy appears to do this by increasing the ability of cancer cells to take up calcium ions, which nerves need to grow and transmit pain signals to the brain. “The idea is that cancer cells basically act as a sponge for all the local calcium, and that depletes the calcium available to nearby sensory neurons,” Hwang says. More research is needed to determine exactly how nanotherapy can alter calcium uptake in cancer cells, which could reveal ways to more effectively target this potential pathway, Hwang says.

In another experiment, the team found that the nerves surrounding the tumor actually helped it grow, suggesting that the nerve-related effects not only eased the pain but also slowed the growth of the tumors — though it’s unclear to what extent, Xiang says.

Together, these findings support the growing idea that targeting the nervous system could revolutionize cancer treatment, Hwang says. But it’s generally easier to treat cancer in mice than in humans, in part because of differences in the anticancer immune response of rodents and humans, he says. Xiang hopes to begin human trials within five to ten years.

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