ProAgio, a drug developed by Georgia State University biology professor Zhi-Ren Liu and his team, is effective in treating pancreatic cancer and surviving in mice, according to a study published in the journal Cellular and Molecular Gastroenterology and Hepatology.
Second study, published in the Journal of Experimental Medicine, showing that the drug is also effective against triple-negative breast cancer, a type of breast cancer that develops rapidly and is difficult to treat with a poor prognosis.
ProAgio, produced from human protein, targets the αVβ integrin cell surface receptor ?, which is expressed on cancer-related fibroblasts. Fibroblasts are cells that generate collagen and other fibrous molecules and can be transported to a tumor, creating a thick, physical barrier called the stroma, which protects the cancer and helps it grow. The drug works by inducing apoptosis, or programmed cell death, in cancer – related fibroblasts that express αVβ integrin ?.
The thick fibrotic stroma that makes pancreatic cancer, which has a five-year survival rate of just eight percent, is so deadly and difficult to treat. Among triple-negative breast cancer patients, research shows that closer stroma is associated with worse survival and higher recurrence rates.
All hard tumors use cancer-related fibroblasts, but in pancreatic cancer and tri-negative breast cancer, the stroma is so dense that there is often no way for conventional drugs to pass through and the cancer. handled effectively. “
Zhi-Ren Liu, Professor, Georgia State University
The stroma also helps the tumor to hide from your body’s immune system. Immunotherapy, a type of treatment that uses your immune system to fight cancer, is less effective against tumors protected by a dense stroma that is rich in cancer-related fibroblasts.
Cancer-related fibroblasts stimulate angiogenesis, or the development of new blood vessels. Angiogenesis plays an important role in the spread of cancer because solid tumors need a blood supply to grow. In both studies, Liu and his team show that roAgio has a significant effect on tumor vasculature. In the case of pancreatic cancer, it opened blood vessels that had collapsed due to excessive extravascular pressure caused by the congested stroma. In the case of triple-negative breast cancer, the anti-angiogenic activity of the drug reduced irregular, leaky angiogenic tumor vessels. In all cases, ProAgio allowed drugs to reach the cancer effectively.
The drug Liu is unique in that it targets only cancer-related fibroblasts – a subclass of cells that are actively involved in supporting cancer – rather than inactive fibroblasts. This reduces the side effects of the drug and increases its effectiveness.
“When you have an injury, for example, normal fibroblasts empty a fiber to limit the damage and promote healing,” Liu said. “The area of the tumor is an injury that will not heal. Quiescent fibroblasts may play a role in preventing cancer from spreading. You don’t want to kill the good guys, just the bad guys. “
ProAgio is licensed to ProDa BioTech, a pharmaceutical research company founded by Liu. In 2018, ProDa BioTech received $ 2 million from the National Cancer Institute to fund toxicology and pharmacokinetic studies necessary before moving the drug to early clinical trials. These studies have been completed and the company has submitted a New Drug Research Application (IND), a request for permission from the Food and Drug Administration to administer ProAgio to human subjects.
Once the IND is implemented, Liu says the next step is to start clinical trials. The first trial, to assess patient endurance and the recommended phase II dose, will begin in early 2021 at the National Institutes of Health Clinical Center in Bethesda, Md., And will be led by Christine Alewine, MD, oncologist at the National Cancer Institute. At the end of 2021, Emory University is ready to begin multicenter testing among breast cancer and pancreatic cancer patients.