*Note to readers: Enjoy this previous article by Dr. Jack Brown, who was unavailable this week.
Pancreatic cancers are notoriously hard to treat, and survival rates are near the lowest for any type of cancer. Any news that may give science a weapon against this dreaded disease is exciting, and the scientific community is now abuzz with a recent publication out of Tel-Aviv University.
The article that has stirred the scientific community is titled “The phenanthrene derivative PJ34 exclusively eradicates human pancreatic cancer cells in xenografts,” and it was published in the journal Oncotarget. In short, the research team transferred human pancreatic cancer cells into a mouse model and then injected the PJ34 molecule into the mice for 14 days. They witnessed an 80% to 90% reduction in pancreatic cancer cells in the mice, with one mouse even seeing a 100% reduction.
Now that makes headlines for sure, but will it transition into a human treatment, and exactly what is this PJ34 molecule?
PJ34 is a pretty small molecule made of only 39 atoms with the chemical formula C17H17N3O2. It’s not new to science, and if you keyword search it in Google Scholar, you will get a few thousand hits. PJ34 has been used in the treatment of strokes and a variety of cancers already like T-Cell Leukemia and BRCA breast cancers. PJ34 belongs to a class of molecules known as PARP1 inhibitors.
PARP1 is short for Poly-ADP-ribose polymerase, and it functions as a DNA repair mechanism in your cells. DNA gets damaged all the time, but cells have evolved a variety of tools to fix the damage. PARP1 is very active when cells are dividing since a good deal of DNA damage occurs during this process.
DNA is the instructions for all cell functions. It usually is pretty well protected in the nucleus, but when a cell needs to divide, the DNA is no longer in that safe house. It gets fully exposed to the cellular environment and often damaged. Since PARP1 is a significant player in fixing the damages that occur, then inhibiting it would allow the damage to remain or go unrepaired.
Cells will actually kill themselves when DNA gets too damaged via a process known as apoptosis or programmed cell death. So, if molecules like PJ34 can block the DNA repair function, then those cells will accumulate more damage and will enter into their programed cell death mode. Combining the use of molecules that block DNA repair mechanisms with DNA damaging chemotherapy or radiation could also be beneficial.
This new article shows that PJ34 can also interfere with NuMA (Nuclear mitotic apparatus protein), which is vital in building the mitotic spindle in dividing cells. The spindle plays several significant roles in cell division, and when it is not working correctly, cells enter into apoptosis also. Once again, PJ34 has caused the cell to kill itself.
The hope is that science could use molecules like PJ34 exclusively to kill the cancer cells, and that is basically the title of this new paper, so it is fascinating news. The tiny PJ34 molecule is proving to be a game-changer in more than one way, be it PARP1 or NuMA inhibition.
Having an effective and specific treatment for pancreatic cancer would be a game-changer, but PJ34 may prove to be an effective treatment in many other cancers as well.