Deep Ocean Drug Discovery

Researchers at the FAU Harbor Branch Oceanographic Institute Marine Biomedical and Biotechnology Research Program aim to use marine biotechnology to improve medicine and help save lives.

“Natural products are small organic molecules made by plants, animals and microorganisms, which are not essential to sustain life but provide advantages to the producing organisms,” said Amy Wright, Ph.D., research professor at FAU Harbor Branch and principal investigator of the natural products chemistry team. Natural products are used every day as medicines, she said. Since the oceans cover 70% of the planet and hold 50 to 80% of the biological diversity of the planet, it makes sense to expect that new medicines will come from marine sources, she said, including those to treat cancer.

“Cancer is not a single disease, but a collection of hundreds of diseases which share in common that cells in some part of the body are growing uncontrollably, or failing to die, and these cells contain damaged or mutated DNA,” said Esther Guzmán, Ph.D., research professor at the FAU Harbor Branch and principal investigator of the cancer cell biology team.

In one of their projects, the researchers grew triple negative breast cancer cells in 3D cell culture, called spheroids, to identify marine natural products that induce programmed cell death. This led to the identification of compounds that kill the cancer cells. In addition, they found that the compounds show synergy with paclitaxel, a drug used to treat triple negative breast cancer. This means that the combination of paclitaxel and the compounds works better than the simple addition of their individual activities, said Guzmán, which is of importance because patients can become resistant to paclitaxel. The compounds identified can help overcome this resistance. The work was done under a Florida Bankhead Coley Research Program grant. Researchers are in the process of securing more funding to do more work to move these compounds closer to the clinic.

Another project by the team focuses on cancers with mutations in Ras proteins, as these cancers are some of the most aggressive and include lung cancers, the leading cause of cancer death, pancreatic cancers, the fourth leading cause of cancer death, and breast cancers, the second leading cause of cancer death among women, Guzmán said. Mutations in Ras can lead to the activation of unusual pathways to obtain nutrients that are beneficial to the cancer and bad for the patient. The researchers tested materials from FAU's marine natural products library to identify compounds that inhibit these pathways in pancreatic cancer cells. This data was used in a proposal for a newly awarded three-year grant from the Florida Bankhead Coley Research Program to continue the work. Compounds with the ability to inhibit these pathways have the potential to be used in the treatment of pancreatic cancer, as these cancer cells depend on these processes to grow.

Pancreatic cancer cells also express receptors such as FoxP3 and B7-H4 that help the cancer cells evade an immune response, Guzmán said. Researchers are also searching for marine natural compounds that can lower the expression of these receptors. “Restoring an immune response may allow patients to see better clinical responses,” she said.

“Marine natural products have many activities that could help us fight aggressive cancers,” Guzmán said. “Our work aims to identify and investigate them with the intent of having some of them reach the clinic and help cancer patients.”

Note: Wright and Guzman are members of the Memorial Cancer Institute Florida Cancer Center of Excellence.