Pancreatic cancer so far has been able to escape early detection. When it is discovered, it is usually in an advanced stage and difficult to treat.
According to a recent article in Genetic Engineering, the third leading cause of cancer deaths in the United States is pancreatic ductal adenocarcinoma (PDAC). It is a type of exocrine pancreatic cancer that evolves from cells that line ducts (small tubes) in the pancreas. Ninety-five percent of pancreatic cancers are PDAC,
This year approximately 60,000 patients will be diagnosed with PDAC. Eighty percent of these patients will not survive more than twelve months after diagnosis.
One in three patients will see shrinkage in their tumors after treatment with the combination chemotherapy FOLFIRINOX. Presently, it is the only effective treatment for pancreatic cancer. The response lasts for approximately seven months.
These powerful drugs cause severe side effects such as nausea, diarrhea, hair loss, fatigue, and a drop in blood cell counts.
Senior author Dr. Kian-Huat Lim stressed the need for improved therapies to treat pancreatic cancer.
About the New Drug
Washington University Medical School researchers have been testing a drug compound that weakens the cancer cells and causes them to be more sensitive to chemotherapy.
Using mouse models, the researchers found that Aclaris Therapeutics’ drug ATI-450 may possibly mitigate some of the side effects of FOLFIRINOX, which currently treats pancreatic cancer. Aclaris provided ATI-450 for the study.
ATI-450, an MK2 inhibitor, is also in clinical trials as an investigational drug for rheumatoid arthritis. The drug aided FOLFIRINOX in killing pancreatic cancers in mouse models and shrank tumors by almost fifty percent more when compared to chemotherapy as a single agent.
The researchers also noted improvement in survival. Mice that received only chemotherapy lived twenty-eight days on average compared to forty-one days for mice receiving the combination treatment.
An unexpected benefit is that ATI-450 and chemotherapy combined appear to have caused the mice to be healthier than the group that only received chemotherapy. The researchers suspect that the new combination drug can mitigate side effects rather than increase them.
In continuing their studies, the research team discovered a critical role for MK2, a molecule that allows the pancreatic tumor cells to evade the effects of chemotherapy. In effect, MK2 activates a pro-survival mechanism.
Dr. Patrick Grierson is a co-lead author of the study and explained that MK2 inhibits cell death (apoptosis) and prevents tumor cells from being destroyed by chemotherapy.
ATI-450 inhibits MK2. Therefore, the combination is more effective in killing the tumor cells. The drug combination was tested in the lab and in a mouse model that is genetically prone to pancreatic cancer.
Mitigating Side Effects
Medical Oncologist Dr. Hian-Huat Lim Ph.D., a lead co-author, explained that there is always a concern of increased side effects when combining drugs. The researchers monitored blood counts and toxicities of the colon and small intestine and found that there was no increase in adverse events.
Dr. Lim added that many side effects associated with chemotherapy are the result of molecules (cytokines) that cause inflammation. ATI-450 was developed to reduce those cytokines in rheumatoid arthritis. Dr. Lim says that they hope to see the same results with the mouse studies.
The investigation of ATI-450 for pancreatic cancer is ongoing. The researchers plan to test whether the drug plus chemotherapy can be combined with immunotherapies and other investigational treatments.
The team sees potential for the treatment of other cancers including gastrointestinal and colon cancers that are now using the same type of chemotherapy regimens.
