Pancreatic ductal adenocarcinoma (PDAC) is the fourth deadliest cancer and has a five-year survival rate of only 10 percent. PDAC, which accounts for more than 90 percent of pancreatic cancer cases, is known to be resistant to most therapeutic agents, and often the diagnosis is late in disease progression as symptoms are difficult to identify.
Aiming to improve treatment methods and health outcomes of people with PDAC, IU researcher Tao Lu, an associate professor of pharmacology and toxicology at the IU School of Medicine and a researcher at the IU Melvin and Bren Simon Comprehensive Cancer Center, has developed small molecule protein arginine methyltransferase 5 (PRMT5) inhibitors that show significant promise in tumor inhibition in mouse models.
“We discovered that PRMT5 is highly expressed in PDAC, and by showing that inhibiting the protein could reduce the tumor growth in vivo, we have hope to further develop this compound into a novel therapy for PDAC and potentially other cancers with high PRMT5 expression as well,” Lu said. “This is an exciting discovery.”
These inhibitors are instrumental for slowing PDAC progression. The researchers hope they will also alleviate PDAC resistance issues by inhibiting cell signaling that leads to drug resistance.
While there are a few treatment options for PDAC, the therapeutic drugs have considerable toxicity, such as leukopenia and febrile neutropenia, and only provide a median overall survival of 8.5 months. The researchers hope the PRMT5 inhibitor can be used to expand available treatment options for PDAC, such as using this new drug alone or in combination with the current standard treatment options, thus significantly improving quality of life for those affected by this cancer.
By inhibiting PRMT5-mediated production of proinflammatory factors, the inhibitor can also potentially be used to treat colon cancer, which is the second deadliest cancer, as well as inflammation related diseases such as wet age-related macular degeneration.
Lu’s startup, EQon Pharmaceuticals, is further developing the PRMT5 inhibitor with the goal of reaching IND readiness and a phase 1 clinical trial in treating PDAC, other types of cancers, as well as inflammatory related diseases.
Lu has a long-standing relationship with IU’s Innovation and Commercialization Office (ICO) and has worked with the office to move several inventions towards commercialization.
“Before working with ICO, I had no idea how to submit an invention disclosure or how to file a patent application,” Lu said. “ICO was extremely helpful in guiding me through those steps and helping me license my IU technology to my startup. I’m thankful for my ongoing relationship with ICO, and I’m excited to continue furthering my research.”
Bri Heron, technology marketing manager at Indiana University’s Innovation and Commercialization Office, contributed the following story.