Just 7 percent of people diagnosed with pancreatic cancer are still alive five years later. Palbociclib, a drug recently approved for breast cancer treatment, has now been shown to greatly extend the lives of mice with the most common form of cancer of the pancreas.
Trials are already underway for treating pancreatic cancer with palbociclib, but identification of the patients most likely to respond to the drug could greatly improve their accuracy. Dr Marina Pajic of the Garvan Institute of Medical Research, Australia and colleagues studied 550 pancreatic tumor biopsies. In two-thirds they found an activated Cdk4/6 pathway, which appears to be the reason the cells divide unchecked, making them cancerous.
“This was an important clue for us, and we started to look in depth at how best to block the Cdk4/6 pathway,” Pajic said in a statement. “We know that the drug palbociclib switches off the Cdk4/6 protein, so we reasoned that palbociclib might halt the growth of the many pancreatic cancers where this pathway is ‘ON’.”
In Gut, the researchers report on experiments giving palbociclib to mice with Cdk4/6 activated pancreatic cancers. Mice treated in this way survived 100 days longer than those given chemotherapy, and those given both did best of all. If the difference scales up to humans’ longer lives, it would amount to years of extra life.
Moreover, they found that the presence of RB protein provides an easy-to-test indication of whether a pancreatic cancer is Cdk4/6 related or not.
One of the reasons pancreatic cancer is so deadly is that it is seldom detected until it has already spread to other organs (metastasized), so Pajic was particularly excited to see that palbociclib provided major life extensions for mice with metastasized cancers.
Palbociclib has recently been approved by the FDA and regulatory bodies in other countries for the treatment of ER-positive/HER2-negative breast cancers. Pajic told IFLScience that while it is not side-effect free, it is usually better tolerated than alternative drugs. Being still under patent it is very expensive, but it also has a large pharmaceutical company with an incentive to expand its applications, ensuring it is unlikely to languish like many other drugs with potential.
Three clinical trials are already underway to test palbociclib’s effects on pancreatic cancer – one involves Pajic’s co-authors. However, none distinguished the type of pancreatic cancer on enrollment. If, as seems likely, palbociclib doesn’t work for people who have non-Cdk4/6 activated cancers, its effectiveness may be hidden.
Pajic told IFLScience her team is retrospectively testing biopsies of participants for RB levels, which could make the trials far more accurate. She added that several other solid tumor cancers, notably some melanomas and glioblastomas, are suspected of also being driven by the same pathway.