Novel compound shrinks pancreatic cancer tumors, prevents regrowth. Researchers believe that MM41 needs to undergo further modifications before it can be tested safely in humans. Scientists from University College London have developed a chemical compound that has decreased the growth of pancreatic cancer tumors up to 80 percent when tested in mice.
Published in Nature Scientific Reports, the findings indicate that the novel compound – MM41 – inhibited the effect of two major genes found in most pancreatic cancers, namely k-RAS and BCL-2. The research was funded by UK charity, Pancreatic Cancer Research Fund.
Pancreatic cancer is one of the most lethal forms of the syndrome, and is most often fatal. Only three out of every 100 individuals diagnosed live for up to five years or longer, and the survival rate has hardly improved in the last 40 years. Most patients are diagnosed when surgery is not an option any longer, which is the only form of treatment presently, and for those who have the surgery, there is an 80 percent chance of recurrence.
Testing The Novel Compound
MM14 was designed to inhibit faulty genes causing pancreatic cancer. Its mechanism of action was seen to involve targeting tiny knots, known as quadruplexes, which are found distinctly in faulty genes.
Headed by Professor Stephen Neidle, a team of UCL researchers performed a small-scale trial consisting of two groups of eight mice with pancreatic tumors. Both the groups were administered different dosages of MM41 over a period of 40 days, twice a week (a total of 12 doses). A control group was also set up which received no MM41 treatment.
It was seen that the group receiving a larger dosage of the compound showed an average decrease of 80 percent in their tumors during the course of treatment, and after 30 days, re-growth of the tumor had ceased in all mice. Furthermore, the tumor was seen to completely disappear in two mice, which received the larger dose, with no signs of re-growth after the treatment was completed, and for an additional 239 days as well – the approximate natural life span of a mouse.
After analyzing the treated tumors, researchers saw that the cancerous cells had taken up MM41 into their nuclei. This demonstrates the ability of the compound to specifically target pancreatic cancer tumor cells. Moreover, the team saw no significant side effects of the treatment, such as organ or tissue damage, and none of the mice exhibited major weight loss.
“This research provides a potentially very powerful alternative approach to the way that conventional drugs tackle pancreatic cancer, by targeting a very specific area of the DNA of faulty genes,” explained Neidle. “One of the genes that MM41 blocks – the BCL-2 gene – is involved in regulating apoptosis, the body’s natural process which forces cells to die if they become too damaged or unhealthy to be repaired. BCL-2 is present in high amounts in many tumors and helps cancer cells to survive, but when the BCL-2 gene is blocked by MM41 in mice, the cancer cells succumb to apoptosis and die.”
Use In Humans?
Although the results of the trial are promising, researchers believe that MM41 needs to undergo further modifications before it can be tested safely in humans. The team is working on optimizing this class of compounds so that it can, one day, be used to treat pancreatic cancer in humans.
Maggie Blanks, Pancreatic Cancer Research Fund’s CEO, stated that the bleak prognosis of pancreatic cancer has led to a more focused funding strategy to find an alternative and effective treatment. To find a potentially effective method to treat and manage pancreatic cancer via MM41 is definitely an exciting and promising development.