A new drug designed to treat pancreatic cancer has recently shown promise in clinical research, as per researchers from the University of Michigan Rogel Cancer Center. This phase 1 clinical trial tested the efficacy of AZD1775, an inhibitor of the Wee1 enzyme. This enzyme plays a key role in repairing damaged DNA. A study summarizing these findings was recently published in the Journal of Clinical Oncology.
This research team’s work builds on a strong foundation of University of Michigan research focused on enhancing pancreatic cancer treatment. For nearly 20 years, researchers at the school have been conducting research to help these patients whose cancers are too advanced to be remedied by surgery.
Standard pancreatic cancer treatment involves the damaging of DNA through radiation and gemcitabine, a chemotherapy drug. Cancer in the pancreas often repairs this induced damage through several acquired mechanisms, allowing the malignancy to persist through such treatments. Led by Meredith Morgan, Ph.D., this Rogel Cancer Center research team found that AZD1775 counteracts this cancer adaptation while leaving the normal, healthy cells perfectly intact.
“If we can disable the DNA damage response in pancreatic cancer cells, it might eliminate treatment resistance and sensitize the cancer to the effects of both radiation and chemotherapy,” explained lead author Kyle Cuneo, M.D., associate professor of radiation oncology at Michigan Medicine.
Morgan and colleagues enrolled 34 participants in the trial, each with locally advanced pancreatic cancer. In addition to the traditional radiation and gemcitabine chemotherapy treatments, these patients also received AZD1775 to test how the drug could supplement existing therapies. The team found that this combination of drugs and radiation resulted in improved patient survival rates.
Pancreatic cancer is notorious for its ability to metastasize, or spread throughout the body. Metastases stemming from pancreatic cancer are part of the reason that this disease has an overall five-year survival rate of just 9%.
“If we’re ever going to cure pancreatic cancer, we’re going to need effective systemic treatment as well as local therapy,” claimed study author Ted Lawrence, M.D., Ph.D., Isadore Lampe Professor and chair of radiation oncology at Michigan Medicine. “Our data suggests that AZD1775 can do both.”
The median length of survival in this clinical trial’s participants was 22 months, with the disease showing no progression for a median of nine months. Previous research regarding the use of gemcitabine alone in patients yielded overall survival of only 12-14 months.
“Adding AZD1775 to radiation and gemcitabine was relatively well tolerated with encouraging survival results. Further studies with this promising combination are needed,” Cuneo concluded.
AZD1775 is currently being investigated for use in other cancer types as well, such as ovarian and breast cancers. This drug is not yet approved by the FDA, but the researchers are working to conduct a follow up phase 2 clinical trial to further solidify their data.
— J Clinical Oncology (@JCO_ASCO) August 14, 2019