At the molecular level, cancer is strikingly similar to a wound that never heals. By understanding more about the mechanisms that wound healing and cancer have in common, researchers hope to find ways to turn cancer from a death sentence into a treatable disease.
Cancer biologist Yejing Ge joined the faculty at The University of Texas MD Anderson Cancer Center. She was recruited in 2018 from Rockefeller University, where she was a postdoctoral researcher, with the help of a First-Time Tenure-Track Award from CPRIT.
All human tissues maintain stem cell populations to replenish differentiated cells when they die, or when injury causes damage. In response to an injury, stem cells spring into action, activating genes that allow them to become specialized cells, like rebuilding the outer layer of skin, for example, after a cut.
Intriguingly, researchers have found that many of the same genes involved in tissue regeneration are expressed in cancers as well. Further evidence for the association between non-healing wounds and cancer, Ge says, are many correlations between patients who suffer from chronic diseases, like pancreatitis or Barrett’s Esophagus, and those who later develop cancer of that particular organ site.
Using the skin of a mouse as a model system, Ge is studying the genes that are activated when the mouse skin heals from a surgical incision or from squamous cell carcinoma, a common cancer of the skin (as well as other organs, such as head and neck, esophagus, lung, and cervix).
“When the cells get stressed and activated to repair wounds,” Ge says, “they are using mechanisms specifically to cope with stress, which are not mechanisms you typically see in normal, healthy tissue.” Ge speculates that cancer cells hijack some of these repair mechanisms in order to support their malignant development.
What’s most intriguing about this similarity is that researchers could target these mechanisms for interventions, while sparing normal, healthy tissue, and avoiding collateral damage. Many cancer treatments are devastating to normal tissues, because those tissues have highly proliferating cells, Ge says. “But the stress mechanisms that we are interested in really differ from normal tissue maintenance mechanisms, so this will give you a handle on how to target cancer specifically without all the collateral damages.”
Ge also notes that in wounded tissue there are many genes that are activated to drive the cells toward differentiation, that is, from stem cells into specific types of tissues; and these genes are completely absent from cancer cells. “You could see if you could force those differentiation pathways in cancer, and drive it into a pathway that is much more mild and much less malignant,” she says. “And that’s very different from blindly going to the cancer and trying to kill everything. This type of treatment could be much more efficient.”
Aggressive cancers are formed of stem cells that derailed from the pool of cells that otherwise normally replenishes tissue after loss or injury, creating new tissue where none was lost. “If you can promote the cancer to go on the route of normal tissue differentiation,” she says, “then you might be able to keep the cancer in a more quiescent state and restore the balance between tissue loss and regeneration.”
Ge pioneered a technique that allows her to relatively quickly observe the effects of gene editing in mice, allowing her to sift through genes and gene combinations efficiently.
Ge was an undergraduate at Tsinghua University in China, and received her Ph.D. from the University of Illinois, Urbana-Champaign. She began as a postdoctoral fellow at Rockefeller University in 2013. She holds a patent for her work at Rockefeller with mentor Elaine Fuchs and coworker Rene Adam.
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