ProAgio, a drug developed by Georgia State University biology professor Zhi-Ren Liu and his team is effective at treating pancreatic cancer and prolonged survival according to a study published in the journal Cellular and Molecular Gastroenterology and Hepatalogy.
A second study published in the journal of experimental medicine shows the drug is also effective against triple-negative breast cancer, a fast-growing and hard-to-treat type of breast cancer that carries a poor prognosis.
ProAgio, created from a human protein targets the cell surface receptor integrin which is expressed on cancer-associated fibroblasts. Fibroblasts are cells that generate collagen and other fibrous molecules and can be mobilized into service by a tumour creating a thick physical barrier known as the stroma which protects cancer and helps it grow. The drug works by inducing apoptosis or programmed cells death in cancer-associated fibroblasts that Express integrin.
The dense fibroid stroma is what makes pancreatic cancer which has a five years survival rate of just eight percent, so lethal and difficult to treat. Among triple-negative breast cancer patients research shows denser stroma is associated with poorer survival and high recurrence rates.
Liu said, all solid tumour use cancer-associated fibroblasts but in pancreatic cancer and triple-negative breast cancer, the stroma is so dense there’s often no way for conventional drugs to penetrate it and effectively treat cancer.
The stroma also helps the tumour hide from your body’s immune system; Immunotherapy, a type of treatment that uses your immune system to fight cancer is less effective against tumours protected by a dense stroma that is rich in cancer-associated fibroblasts.
Cancer-associated fibroblasts promote angiogenesis or the development of new blood vessels, Angiogenesis plays an important role in the spread of cancer because solid tumours need a blood supply to grow in both studies, Liu and his team show ProAgio has a profound effect on tumours vasculature in the case of pancreatic cancer, it reopened blood vessels that had collapsed due to high extravascular stress caused by the dense stroma in the case of triple-negative breast cancer. The drugs anti-angiogenic activity reduced irregular leaky angiogenic tumour vessels. In both cases, ProAgio allowed drugs to effectively reach cancer.
Liu’s drug is unique in that it targets only cancer-associated fibroblasts- a subclass of the cells that are actively engaged in supporting cancer rather than inactive fibroblasts, this reduces side effects of the drug and increases its effectiveness.
“When you have a wound, for example, normal fibroblasts will secrete fibres to limit the damage and promote healing,” said Liu. “The tumour region is basically a wound that won’t heal. Quiescent Fibroblasts may play a role in preventing cancer from spreading; you don’t want to kill the good guys only the bad guys” he added.
ProAgio is licensed to ProDa Bio Tech, a pharmaceutical research company founded by Liu in 2018. ProDa Bio Tech received $2 million from the National Cancer Institute to fund toxicology and pharmacokinetics studies that are required before moving the drugs to early-stage clinical trials. Those studies have been completed and the company has submitted an Investigational New Drugs (IND) Application, a request for authorization from the Food and Drug Administration to administer ProAgio to human subjects.
Once the IND is granted, Liu says the immediate next step is to begin clinical trials, The first trial is to determine patients tolerability and recommends phase if dose, will begin in early 2021 at the National Institute of Health Clinical Centre in Bethesda, Mdi and will be led by Christine Alewine M.D an oncologist at the National Cancer Institute in late 2021, Emory University is set to begin a multi-site trial among breast cancer and pancreatic cancer patient.
By: Peace Chigozie