It turns out, the originating source of some cancers is leftover embryonic cells found in every adult. Findings of a new study by American and Asian scientists may turn general perceptions about certain cancers on its head.
The general assumption in cancer development is that normal cells grow out of control and become hazardous. But for deadly esophageal cancers, new research traces the precursor to these leftover embryonic cells triggered by gastric reflux disease, also called GERD or “chronic heartburn”.
“A lot of cancers you can do little about, and currently new drugs are approved based on their ability to extend life by one or two months,” said the study’s senior author Frank McKeon of Harvard Medical School and the Genome Institute of Singapore. “Focus on cancer precursors may be our best hope for medicine. Here, we are looking at a cancer precursor that is present in all of us.”
Some people with GERD have a greater risk of developing esophageal cancer. These patients often have Barrett's esophagus, a condition in which intestinal-like cells appear in the esophagus. Esophageal cancers are difficult to treat. As such, gastric cancer death rates have remained relatively unchanged over the past 30 years, and gastric cancer continues to be the second leading cause of cancer-related death globally, according to a 2005 study published in the Annuals of Surgery.
“It's not clear that the embryonic stem cell precursors have any real purpose,” says study author Wa Xian. “Methods to rid the body of those cells may therefore be the easiest and most cost-effective way to stop the disease before it even starts, particularly for those at the greatest risk.” The study is published in the June 24, 2011 edition of Cell.
The prevailing theory has been that the abnormal cells seen in Barrett's esophagus arise as the normal squamous stem cells are damaged in response to acid-reflux and transform themselves into new, intestine-like cells. Using a mouse model of chronic acid-reflux disease, Xian and McKeon now show that conclusion may be debunked. Even as embryos, the study animals showed a vast expanse of intestine-like cells in their esophaguses with gene expression profiles very similar to those seen in Barrett's.
"The metaplasia [replacement process of one cell type for another] developed very quickly, in a matter of days," Xian said. "This was shocking to us as we generally consider cancer precursors taking multiple genetic 'hits' and years to develop."
The speedy development suggested that the precancerous condition wasn't related to the slow accumulation of mutations. Their findings also argue against the idea that the normal stem cells were undergoing a change of fate.
The dim prognosis for esophageal adenocarcinoma has driven therapeutic strategies aimed at destroying Barrett's esophagus, including Radio Frequency Ablation (RFA), before it progresses to aggressive cancer," said McKeon."While RFA appears to be exceedingly effective in the short term, there are hints that Barrett's might be fairly resilient and poised for recurrence.”
McKeon and Xian say they suspect an additional subset of cancers, especially those linked to inflammation and tissue damage, might arise from precursors similar to Barrett's. "If so, we anticipate rapid progress into a group of particularly aggressive cancers that typically outwit the best treatments we have."
The new findings suggest it may be more effective to go after the precursor cells instead. To do this, Xian says they “will have to clone the stem cell for Barrett's and the Barrett's precursor cell in the junction to find the targets needed to eradicate them.”
Lynette Summerill is an award-winning writer who lives in Scottsdale, Arizona. In addition to writing about cancer-related issues for EmpowHER, her work has been seen in newspapers and magazines around the world.
Cell Press. Residual Embryonic Cells as Precursors of a Barrett's-like Metaplasia. Wa Xian, Frank McKeon et al. Volume 145, Issue 7, 1023-1035. 24 June 2011.
National Cancer Institute. Gastric Cancer. Accessed at : http://www.cancer.gov/cancertopics/pdq/treatment/gastric/HealthProfessional/page1/
Annuals of Surgery. Gastric Adenocarcinoma: Review and Considerations for Future Directions.2005 January; 241(1): 27–39. doi: 10.1097/01.sla.0000149300.28588.23. Abstract accessed through National Cancer Institute: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1356843/
National Cancer Institute. Barrett’s Esophagus. 2009. Accessed at:
Leftover Embryonic Cells Connect Gastric Reflux and Cancer
Reviewed July 19, 2011
by Michele Blacksberg R.N.
Edited by Shannon Koehle