Yesterday I managed to get to see a fabulous talk by Dr. Edison Liu, President and CEO of The Jackson Laboratory in Maine. I was able to squeeze it in, in between working on my R01 proposal and preparing for teaching histo to the med students here at UC Davis Med School.
Dr. Liu was a keynote speaker at the UC Davis Comprehensive Cancer Center Symposium (see pic at right).
His talk was entitled “Systems Biology in Cancer Genomic Medicine: Lessons from the Long Tail”.
Dr. Liu covered a great deal of ground in his talk in terms of specific oncogenic events in cancer, particularly breast cancer. All of it was great.
However, I was particularly fascinated by his discussion of the “long tail” concept.
What is the “long tail” of cancer?
What Dr. Liu meant, at least my take on it, is that while some oncogenic events such as certain mutations (e.g. BRCA1/2 in breast cancer) or specific DNA characteristics called SNPs that we all possess in different forms, are relatively famous and well-known to be linked to cancer, these “star villains” of the cancer world still only account for a relatively small fraction of cancers.
How do the rest of the cancers get caused?
On a bar graph of all the known things linked to cancer, the cancer “star villains” such as BRCA1/2 stand out with relatively tall bars, but in such a graph there are many many other cancer-related events that each individually are linked to relatively few cancers (say only 1%)…so in our graph, you see a host of smaller bars heading off toward the right on the X axis.
Collectively these “lesser” events “tail” off in the graph from the big bars for the oncogenic bad guy stars’ bars. Dr. Liu calls these the “long tail. This “tail” makes a major contribution to cancer. In this way these more rare mutations are still very important.
Often what happens in the events that lead up to cancer is that many different steps have to happen to go from a normal cell to a dangerous cancer cell. Only together do these steps trigger cancer and frequently it is a cocktail of relatively rare events that in combination provide the power to cause cancer. In science we call this a “combinatorial” process.
Even though collectively cancer (in the umbrella term sense of the word) is a relatively common disease, in human cells many things have to go wrong to make cancer so we are in a sense lucky compared to some other species such as mice because mouse cells are very easy to turn into cancer. Of course mice do not typically live long enough in the wild to get cancer.
It is by understanding not only the star villains of cancer, but also the long “tail” of smaller, but still important players that we’ll unlock the mechanisms behind cancer and that is the road to new treatments.