New drug attacks tumors in animal trials: study
The researchers targeted a protein called retinoid X receptor (RXR), which is abundant in sarcoma and other cancer cells but has low concentrations in healthy cells.
They computationally screened more than 20,000 compounds, narrowed the field to a handful of candidates, picked the most promising one to synthesize in the lab, and designed a nanoparticle within which the drug candidate could be packaged for transport and delivery inside the cancer cells.
The researchers tested the compound for efficacy and toxicity, first in tissue cultures in the lab, then in mice with tumors that formed from injected cancer cells, then in cancer-susceptible pigs that had developed sarcomas of the skin.
They found that the new drug candidate was more than three times more effective than currently available drugs. Not only did the tumors shrink, but the cancer cells were less likely to multiply and were less mobile, reducing their ability to spread to other tissues.
"We saw that the tumor was shrinking," said study leader Dipanjan Pan, a UI professor of bioengineering. "Interestingly, the mouse and the pig tumor data correlated with each other, and both of them corroborated our hypothesis. The drug is acting the same way in completely different species."
Though the researchers did not see any significant toxic activity, they did observe minor side effects that seemed to subside over time. Further study is needed to determine side effects and effective dosages.
In the next step, the researchers plan to conduct a clinical trial in dogs with osteosarcoma. Dogs develop such tumors spontaneously, as humans do, and treatment is difficult. The researchers also plan to increase dosages to see what concentration is the safest and the most effective, and to further investigate any side effects or toxicities.