Question: What obstacles does the unique genetic composition of human cancers pose to treatment, and how can they be overcome?
Gregory Hannon: Although each cancer is unique, there are certain core pathways, biological modules in essence, that are altered in nearly every cancer cell. And the number of those modules expands as one gets more specific to a particular subtype; let’s say estrogen receptor positive breast cancer. So, the notion, and this is one of the ways in which RNAi is being deployed very powerfully, is to try to correlate the vulnerabilities that are created by the inactivation in those individual biological models and then exploit that vulnerability for therapy. The way that you can think about this is that cells are designed or evolve to be robust. And every time you take away one of these biological modules, these pathways, it affects the robustness of cells. Think about a Jenga tower, and you’re pulling blocks out of a Jenga tower. The more blocks that you pull out, the easier it is to make that tower fall. And what people are doing with RNAi is trying to figure out precisely what additional block to pull out to make that tower fall. Where the tower wouldn’t fall if one had a normal cell which essentially has homeostatic mechanisms to be robust, to resist the biological difficulties that would be created by the loss of the pathway that would represent that key therapeutic target. So, the idea is to exploit common aspects of the genetics to create therapies that overcome the individuality of the disease.
Recorded on February 9, 2010