Image of pancreatic adenocarcinoma. Recent studies have found that mutations slowly accumulate in the DNA of pancreatic cancer cells over a long period of time.
A patient newly diagnosed with pancreatic cancer can expect a particularly bleak prognosis of no more than two years. No exception to this rule, actor Patrick Swayze (the star of one of my all time favorite movies, Dirty Dancing) succumbed to pancreatic cancer just 20 months following diagnosis. In his and most cases, the key problem is that by the time the cancer is detected it is already in an advanced stage. Soon afterward it begins its rapid spread to other organs and, by that point, curative options are few. This has led many to wonder whether pancreatic cancer is an especially aggressive disease or if the current methods of detection do not allow for early enough diagnosis.
November is Pancreatic Cancer Awareness Month and to kick it off, two new studies published in the journal Nature find that pancreatic cancer is actually not swift-moving. In fact, the time between formation of the primary tumor to the patient’s death can span 21 years or longer. This reveals a whole new, and much larger, window of time for early diagnosis and therapy.
The two research teams studying this hidden timeline of pancreatic cancer were led by Shinichi Yachida and Christine Iacobusio-Donahue from Johns Hopkins University and Peter Campbell and Andrew Futreal from Wellcome Trust Sanger Institute. Both research groups utilized the latest high-throughput, high-resolution sequencing techniques, allowing them to rapidly read every gene - a sequence of DNA known to code for a certain function - in great detail.
Using this technology, they were able to closely compare the DNA sequences from cells in primary pancreatic tumors to the DNA sequences of cells from secondary tumors in nearby organs, following metastasis. Yachida and Iacobusio-Donahue’s group traced the changes in DNA throughout the cancerous stages and discovered that the primary tumors slowly accumulate a surprisingly large number of mutations in their DNA before secondary tumors form. Knowing the average amount of time it takes for a mutation in DNA to occur by random, the researchers were able to back calculate the approximate time of the cancer’s inception. They discovered that at least 10 years pass between the rise of the first cancer cell and the ability of the cancerous cells to spread. It’s another five years before the cells actually begin to mobilize.
Scientists at Sanger Institute also traced the genetic evolution of pancreatic tumors but focused on larger-scale rearrangements of chromosomes (the structures found in cells that contain DNA and associated proteins) such as deletions, insertions and translocations of genetic material. The key finding from Campbell and Futreal’s team was that, of the genomic rearrangements identified, more than half were found in both primary and secondary tumors. The results from both research groups point to the fact that widespread genomic instability begins during the earliest stages of cancer, long before the disease becomes clinically evident and obstinately fatal.
While it may be too late for Patrick Swayze, the hope is that these studies will soon provide new opportunities for earlier detection of pancreatic cancer. With the rapid advancement of genome sequencing and genome-wide screens, that day may not be far off.