Robert A. Nagourney, M.D.
It was during the last weeks of December that a particularly interesting article crossed my desk. The study done by a group from Toronto, Canada, is entitled Variable Clonal Repopulation Dynamics Influence Chemotherapy Response in Colorectal Cancer. The study examined the proliferative capacity and drug sensitivity in colorectal cancer cells that were tracked using a process known as lentiviral lineage tracking. The investigators showed that despite serial passages, the cell populations remained stable from a genomic standpoint.
What was most interesting was the finding that these genomically related subpopulations became progressively more resistant to oxaliplatin after drug exposure, suggesting what they described as “inherent functional variability.”
As one of several investigators engaged in the field of functional profiling, I found the article both interesting and extremely consistent with our laboratory observations. First, cancer cells display biological differences that may reflect environmental (microenvironmental) influences, epigenetics and other drivers not readily identified at the DNA level.
Second, these investigators, using extremely sophisticated molecular techniques, found, as the lead investigator said, “We should not be putting our eggs exclusively in the genetics basket.” This quote from the lead investigator, John Dick, was particularly resonant.
As many of you who read my blogs know, a recurring theme in these pages is the need to broaden our scope and examine the protein, metabolic and functional characteristics of the cancer cells in their native state. Once again we find that as our most accomplished molecular brethren drill down to the bedrock of cancer biology, they are confronted by complexities and crosstalk that can only be effectively studied at the level of cell biology.
http://www.the-scientist.com/?articl...-Its-Genetics/