One form of pancreatic cancer has a new enemy: a two-drug combination that inhibits tumors and kills cancer cells in mouse models.
For the first time, researchers have shown that a certain protein becomes overabundant in pancreatic neuroendocrine tumors, allowing them to thrive. They also found that pairing a synthetic compound with an existing drug provides a more effective anticancer punch than a single drug. The findings were published in the Journal of the National Cancer Institute.
Finding new treatments is critical because less than 5 percent of patients with pancreatic neuroendocrine tumors respond to everolimus, the most commonly used pharmaceutical. Neuroendocrine tumors, which form in the hormone-making islet cells, account for 3 percent to 5 percent of pancreatic malignancies and have a five-year survival rate of about 42 percent, according to the National Cancer Institute.
The researchers discovered that a single protein is behind the process that allows pancreatic neuroendocrine tumors to thrive. The protein, known as focal adhesion kinase, or FAK, activates an enzyme called AKT, which helps islet cells in the pancreas to survive. But when islet cells begin turning into tumors, the FAK protein gets overproduced, researchers found. This overabundance of the protein allows tumors to resist chemotherapy and evade efforts to kill them off.
After identifying FAK's role in tumor development, the researchers started looking for ways to get it in check. One idea was finding something to make the antitumor drug everolimus more effective. Among the substances they tested was a synthetic, small-molecule compound known as PF-04554787. During lab testing, the compound "markedly inhibited" the growth of three human pancreatic cancer cell lines five days after treatment and induced the death of pancreatic cancer cells. Researchers then tested its effectiveness on human pancreatic cells that had been implanted in mouse models. Daily doses of the compound reduced tumor volume by about 50 percent after 25 days, they found.
Next, researchers paired the compound with everolimus. While everolimus can extend some patients' lives by holding tumors in check, it does little to make them regress and is not effective for many people. The research team found that combining PF-04554787 together with everolimus killed off pancreatic cancer cells more effectively than everolimus alone. In testing on two mouse cell lines, the drug combination reduced the viability of cancer cells by about 50 percent when compared with everolimus alone, according to the findings.
The findings also have potential uses for most other types of solid tumors, including those affecting the lungs and ovaries, where the same protein and enzyme are involved.
Based on material originally posted by University of Florida.