By Wendy Sarubbi | September 19, 2018 10:09 am

Pancreatic cancer has the worst survival rate of any major cancer and a team of UCF College of Medicine researchers is developing a novel therapeutic to slow the cancer’s growth and increase survival.

Drs. Deborah Altomare a cancer researcher in the Burnett School of Biomedical Sciences,  and Otto Phanstiel, a medical education professor and medicinal chemist,  received an $800,000 grant from the Florida Department of Health’s Bankhead Coley Cancer Research program to develop and test drugs that essentially starve pancreatic tumors.

The researchers are developing drugs that attack polyamines —small molecules in the body that can act as growth factors for tumors. Cancer cells rely on polyamines to sustain their rapid growth. Drs. Altomare and Phanstiel are creating a combination treatment of two inhibitor drugs. The first blocks the “factory” inside the cell where polyamines are made. The second locks the “door” or pathway that tumor cells use to import polyamines. With no way to produce or receive polyamines, tumors are effectively starved of the building blocks they need to grow.

“Without polyamines, they basically stop growing and depending on their susceptibility, some tumor cells may die,” said Dr. Altomare, who is currently testing the combination therapy on animal models.

While the therapy blocks out polyamines, it also helps the body’s immune system attack the tumors.

“The really exciting thing about this strategy is that it not only depletes tumors of the polyamines they need to grow, but also unleashes the immune system to kill these tumors,” said Dr. Phanstiel, who has been researching polyamines since 1991.

“We believe that pancreatic tumors use polyamines to create an immune shield around themselves that keeps tumor-killing immune cells away. Our therapy removes this immune shield and allows tumor-killing immune cells better access to the tumor.”

“In short, we have developed a novel chemotherapy which doubles as an immunotherapy,” he added. “This therapeutic approach is a double-whammy for tumors and hopefully it will make a difference for patients diagnosed with this deadly disease.”

The team is also collaborating with Drs. Pablo Arnoletti and Sally Litherland, oncologists at Florida Hospital, to look at the therapy’s effects on patient samples, particularly metastatic cancer cells that have broken away from the original tumor and are spreading.

Pancreatic cancer ranks third in the number of cancer-related deaths in the United States, after lung and colorectal cancers. Patients have less than an 8 percent chance of surviving beyond five years after diagnosis. Pancreatic cancer is difficult to detect and diagnose, primarily because there are few symptoms in its early stages. By the time the patient has developed symptoms, the cancer has already spread.

Therapies such as chemotherapy can help some patients, but are often quite toxic. Surgery is sometimes an option, but only if pancreatic cancer is diagnosed in in its early stages before it spreads to the liver or other organs.

“Our mission is really to give patients a fighting chance, because this is a really tough cancer for people to survive,” said Dr. Altomare, who has been doing cancer research for nearly 30 years. “The more aggressive it is, the harder it is to fight, and when you get to stage 3 or 4, the chances of surviving are pretty slim.”

Though the grant is specific to pancreatic tumor research, the team hopes their findings will lead to positive therapeutic outcomes for other cancers such as melanoma and breast cancers. They are also looking forward to collaborating with other researchers at the new UCF Lake Nona Cancer Center, set to open soon in the former Sanford Burnham Prebys Research Institute. The comprehensive center will house cancer researchers, clinical trials and treatment for patients.

“The new center will not only give us opportunities to collaborate with other cancer researchers,” Dr. Phanstiel said, “it will offer a new way to bring our technology to clinical trials and help bring hope to patients with this deadly disease.”

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