Pancreatic cancer cells repair their DNA particularly well when damaged by chemotherapy and radiation. This is one of the reasons why standard treatments for the disease are often ineffective. Researchers at the University of Michigan's Rogel Cancer Center are now reporting promising results from an early study of a drug that blocks an enzyme that cancer cells need to repair their own DNA.
AstraZeneca's AZD1775 drug blocks an enzyme called Wee1, preventing pancreatic cancer cells from radiation and chemotherapy. In a study combining AZD1775 with irradiation and gemzar (gemcitabine), 34 patients with pancreatic cancer who were too advanced to be surgically removed had a mean overall survival of 22 months. This was better than a previous trial of Gemzar alone, where survival was only 12 to 14 months.
University of Michigan researchers are currently planning a Phase 2 combination therapy trial. The Phase 1 results, which aimed primarily at determining the appropriate dose of AZD1775, were published in the Journal of Clinical Oncology.
"If we can turn off the DNA damage response in pancreatic cancer cells, it may eradicate treatment resistance and sensitize cancer to the effects of both radiation and chemotherapy," said Kyle Cuneo, Associate Professor of Radiation Oncology at Michigan Medicine, in a statement.
CONNECTION: Prevention of the spread of pancreatic cancer
In 2013, AstraZeneca acquired the rights to Merck's AZD1775. It's one of 250,000 drugs that are part of AZ's Open Innovation Program – a drug library that makes the company available to researchers around the world who want to explore their potential in various diseases.
According to the company, AZD1775 is currently being tested both as a solotherapy and in combination with other medicines for ovarian cancer and various solid tumors. In 2017, AZ formed a collaboration with Combinations Alliance in the UK to test the drug for head and neck cancer. There are currently more than 50 additional AZD1775 trials listed on ClinicalTrials.gov.
Preventing pancreatic cancer cells from repairing their DNA is one of many ideas currently being studied to fight the disease. Last week, a research team at the Garvan Institute in Australia investigated the potential to reduce the protein pearlcan, which facilitates the spread of pancreatic tumor cells to other parts of the body. The combination of a pearlcane lowering drug with chemotherapy could stop the spread of the disease, the team suggested.
Several other treatment regimens are being investigated, including a combination of the Merck checkpoint inhibitor Keytruda with the GlaxoSmithKline RIP1 inhibitor. In mice, this treatment accelerated the activation of immune cells that kill cancer and prompted GSK to start a clinical trial in people with pancreatic ductal adenocarcinoma.
The University of Michigan team, which is currently planning a Phase 2 study with AZD1775, reported that the combination of the medicine with Gemzar and radiation delayed the progression of pancreatic cancer in the Phase 1 study beyond an average of nine months and was well tolerated.