PARP Inhibitors Shows Promise as Treatment for Pancreatic Cancer
by Dr. C.H. Weaver M.D. 9/10/2018
A precision cancer medicine recently approved for the treatment of ovarian cancer in women including with BRCA1 and BRCA2 mutations appears to be effective in the management of some individuals with pancreatic cancer who have the same mutations.
About Pancreatic Cancer
Pancreatic cancer is one of the deadliest forms of cancer and is projected to become the second leading cause of cancer death by 2020. Each year, approximately 43,000 people are diagnosed with pancreatic cancer in the United States and close to 37,000 die from the disease. The disease is often diagnosed at an advanced stage, treatment remains challenging, and new treatment approaches are required. About nine percent of pancreatic patients have a BRCA mutation associated.
About PARP Inhibitors
Not all cancer cells are alike: Cancer cells may differ from one another based on what genes have mutations. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. This “genomic testing” is performed on a biopsy sample of the cancer and increasingly in the blood using a “liquid biopsy”
Once a genetic abnormality is identified, a specific precision cancer medicine or targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.
The poly ADP-ribose polymerase (PARP) enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.
Doctors have reported the results of a small clinical trial evaluating the PARP inhibitor Rubraca® (rucaparib) in 19 pancreatic patients with BRCA mutations. Twenty-one percent of the patients had BRCA1 mutation and 79 percent had BRCA2 mutations. Overall, a clinical benefit from Rubraca® was observed in 32 percent of patients (6/19) treated with Rubraca®, and 45 percent in patients (4/9) who had received only one prior chemotherapy for locally advanced or metastatic disease.
This report demonstrating activity of PARP inhibitors in pancreatic cancer is encouraging and clinical trials evaluating these medicines should be performed in combination with chemotherapy and in earlier stage patients. Individuals with pancreatic cancer should discuss the role of genomic testing and clinical trials with their treating physician.