Funded by the Hearst Foundation
The last 30 years of research have identified more than 500 genes that are mutated (i.e. defective) in human cancer and a lot of attention has been devoted to these mutations. A central mystery that has not yet been solved is why and how the vast majority of cancers show aneuploidy, i.e. the gain or loss of specific chromosomes (chromosome-specific aneuploidy). For example, tumor cells from colon cancer very often (more than 55% of cases) show in their DNA one extra copy of chromosome 13 (normal cells have 2 copies of chromosome 13, cancer cells have 3/4 copies). If scientists are able to understand what are the consequences of chromosome-specific aneuploidy for cancer cells compared to normal cells, then we will be able use this insight to develop new, more effective treatments, i.e. therapies that specifically target cancer cells while sparing normal cells. The goal of this proposal is to unravel this mystery and begin to use this information to design new therapeutic strategies. To accomplish this task, I will be taking a novel approach. First, we will use normal human cells and we will engineer them to contain an extra copy of a specific chromosome. Then we will utilize a series of experiments to comprehensively characterize the biology of the cells containing the chromosome-specific aneuploidy compared to normal cells. We aim to identify molecules that can specifically kill the aneuploid cells compared to the normal cells, in other words we will look for the “Achilles’ heel” of cancer cells.