Could a once-daily oral targeted therapy called a PARP inhibitor be effective in treating pancreatic and other solid tumors with a PALB2 mutation?
Many solid tumors are caused or exacerbated by the body’s inability to repair double-stranded DNA breaks. While BRCA1/2 mutations are the best-known mutations behind the inability to repair these DNA breaks, mutations in other genes, such as PALB2, are also associated with susceptibility to various cancers, including familial breast and pancreatic cancer. Emerging evidence suggests that, similarly to patients with BRCA1/2 mutated cancers, patients with inherited or random PALB2 mutations may benefit from treatment with PARP inhibitors.
What Is a PARP Inhibitor?
PARP stands for poly ADP-ribose polymerase, an enzyme important in repairing small breaks in single DNA strands. When PARP is blocked, small breaks in single DNA strands transform into double-stranded breaks, which can lead to cell death if left unrepaired. By blocking (or inhibiting) this enzyme with a PARP-inhibiting drug, cancerous cells with DNA repair defects (carrying mutations in either BRCA1/2 or PALB2) are less likely to be able to repair DNA breaks. This results in cell death and possibly a slowdown or stoppage of tumor growth, while healthy cells (with intact BRCA1/2 or PALB2) are spared. This type of treatment is called targeted therapy because it attacks only the cancer cells and not the normal cells. In addition, these tumors may also have an increased sensitivity to chemotherapy.
How the Trial Works
To participate in this phase II trial, patients must have solid tumor cancers, including breast, colon, lung, urologic, esophageal, endometrial, head and neck, melanoma, and pancreatic cancer, with a PALB2 mutation. All participants will receive the PARP inhibitor niraparib, taken orally every day. Niraparib has been approved as a maintenance treatment for ovarian, fallopian tube, and peritoneal cancers.
Researchers are looking at how the tumors respond to treatment and how long this response lasts, as well as at the safety of the treatment. We encourage you to consult your physicians for clinical trials that may be right for you. The website ClinicalTrials.gov provides more details about this trial, as well as many others. You can visit the EmergingMed Trial Finder for a list of all active pancreatic cancer clinical trials.