sing that a restricted cell population appears to be the source of new tumor cells – in much the same way as stem cells are the source of mature, differentiated healthy cells.
Senior author Prof. Michael F. Clarke, early pioneer of the idea of cancer stem cells, who among other things heads a lab in Stanford University’s Ludwig Center for cancer stem cell research, explains why they turned to cancer stem cells:
“We reasoned that tumors containing high numbers of cancer stem cells might be associated with a more aggressive disease and wanted to find a way to easily find them.”
Using a new bioinformatics approach, the team searched data from over 2,000 colon cancer patients and found 16 genes whose lack of expression is always tied to high levels of cancer stem cell markers.
Of the 16 potential biomarkers, they found only one – the gene CDX2 – for which a standardized test that detects its expression is already available.
CDX2 regulates cell differentiation – that is, deciding the type of cell an immature stem cell matures into – in the lining of the colon, which is where colon cancer starts.
The team found that colon cancer patients whose tumors did not express CDX2 were more likely to relapse and die, compared with patients whose tumors did express CDX2.
The researchers were surprised by the finding, as Prof. Dalerba explains:
“We wanted to understand if the small group lacking CDX2 expression – approximately 4% of the global colon cancer population – fared poorly because of an intrinsic resistance to chemotherapy. To our surprise, we found that, on the contrary, tumors lacking CDX2 expression, despite being very aggressive from a biological point of view, also appeared to benefit from early treatment with adjuvant chemotherapy.”
Further analysis using data from other projects showed that the finding was also true for stage 2 colon cancer patients; those whose tumors lacked CDX2 expression were more likely to benefit from post-surgery chemotherapy than counterparts whose tumors did express the gene.
Prof. Dalerba says the exciting part of the finding is that “an inexpensive, simple test for CDX2 expression is already widely available,” although it will have to undergo prospective and randomized clinical trials before it is ready for clinicians to use with colon cancer patients.
Meanwhile, Medical News Today recently learned how a gene called Sprouty2 – known to stop tumors spreading in many types of cancer – appears to promote spread in some colorectal cancers.