The traditional model of cancer development considers that tumors arise from a series of sequential mutations resulting from genetic instability and/or environmental factors effecting normal cells. A major argument against this model is the prolonged period required to develop the first mutation that subsequently leads to malignant tumor formation. In many tissues in which tumors arise, mature cells have a short lifespan and a limited opportunity to accumulate the multiple mutations required for tumor development.
More recently, a new model has been proposed, which considers that tissue stem cells undergo mutations that deregulate normal self-renewal pathways, leading to tumor formation. Since stem cells are immortal or have a longer lifespan, they can more easily accumulate mutations. This latter model, supported by recent studies, suggests that tumor formation may result from the deregulation of normal self-renewal pathways of tissue stem cells. The cancer stem cell hypothesis would have profound implications for cancer therapy. Cancer stem cells, like normal stem cells, are more resistant to conventional chemotherapies than other more differentiated cancer cells;
hence, to cure cancer, it is important to target not only proliferating cells but also stem cells. Developing therapies that are selectively toxic to cancer stem cells while sparing normal stem cells may lead to more effective treatment options. And understanding cancer stem cell biology will help in the development of predictive markers and of targeted therapeutic strategies.
At GNF, we are using our technology infrastructure to characterize the cancer stem cells from various tumors and to develop therapeutics capable of eliminating them. Our efforts include understanding the processes that normal stem cells employ and identifying the defects that lead to the development of cancer stem cells. Within our group, we are:
- Isolating and characterizing cancer stem cells from a range of solid tumors and identifying the pathways required for their self-renewal
- Developing relevant self-renewal assays that are compatible with high throughput screening (HTS) format for functional genomic and small molecule screens in order to identify biological networks essential for cancer stem cell's function
- Determining the frequency of non-tumorigenic cancer cells acquiring properties of cancer stem cells
- Functional genomic and proteomic characterization of cancer stem cells and normal stem cells
- Creating a new generation of in vitro assays for the validation of identified oncology targets with a focus on cancer stem cells
- Developing in vivo efficacy models that are capable of interrogating the effect of therapeutics on cancer stem cells.