Studies into the genetic changes that occur in pancreatic cancers show the notoriously deadly disease develops over a longer time than thought, and suggest potential new targets for treatments, according to two reports published today (Oct. 27) in the journal Nature.
Pancreatic cancer is one of the deadliest cancers — this year alone, the National Cancer Institute expects it to be diagnosed in more than 43,000 Americans and to kill more than 36,000.
The high mortality rate is largely due to the fact that the cancer has no early symptoms and has metastasized, or spread to other organs, before it is detected.
How long pancreatic cancer takes to grow
In one of the new studies, Christine Iacobuzio-Donahue of the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins University and colleagues looked at the genetic mutations in tumor samples from seven patients who died of metastatic pancreatic cancer.
The researchers compared the mutations found in the patients' original tumors, and also the mutations found in the organs to which their cancer had spread.
They found all of the mutations in the metastases were present in the original tumor.
By analyzing the mutations, Iacobuzio-Donahue created a timeline of how pancreatic cancer grows. Her results showed 11.7 years pass between the first mutations and the development of true cancer cells, and 6.8 years pass between the arising of the first cancer cells and the development, in at least one cell, of the potential to spread to other organs.
It followed that pancreatic cancer's high mortality rate is not due to rapid spread but rather to the failure to detect its earliest stages, she said. The time the cancer takes to develop provides a “window of opportunity” for diagnosis and treatment.
“This question has not really been answered for other cancer types,” Iacobuzio-Donahue told MyHealthNewsDaily, “but we were able to address it because of our unique approach of performing rapid autopsies to collect the entire primary tumor to compare to the metastases.”
An evolving disease
A separate study took a closer look at the processes at work in the mutations in pancreatic cancer. Peter Campbell of the University of Cambridge in Great Brittan and colleagues found not only do mutations in the tumor in the pancreas cause metastasis, but the metastases themselves may continue to develop further mutations.
“It's a somewhat depressing view of cancer from the therapeutic viewpoint,” Campbell told MyHealthNewsDaily, because this, in a sense, creates a moving target for drugs. “But it does partly explain why metastatic pancreatic cancer has such a dismal prognosis.”
Still, Campbell said organ-specific mutations may be what allow tumor cells to thrive in certain organs, and these mutations could be targets for drugs. For example, in cancer that had spread from the pancreas to the lung, Campbell found that a gene called myc had been mutated. This mutation is what allowed cells to “set up shop in lung tissue,” Campbell said.
Larger studies are needed — Campbell's study included samples from only 10 patients — to determine whether “a core set of genes that promote specific metastases” can be identified, Campbell said.
“I think the most logical step is to treat the earliest mutations,” Campbell said. “It may then be possible to choose therapies to mop up any resistant metastases.”
Still, both studies highlighted not only the complexity of pancreatic cancer mutations within a patient, but also the uniqueness of particular mutations to each individual. More research would be needed to develop treatments.
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