UNC Lineberger member Channing Der, PhD, and postdoctoral researcher Bjoern Papke, PhD, published a review in Science about promising developments in the effort to develop treatments for cancers driven by RAS mutations, which have doggedly evaded scientists’ best offensive efforts.
The review, “Drugging RAS: Know the enemy,” outlined obstacles as well as potential novel approaches to finding treatments targeted against three RAS oncogenes that are part of the most frequently mutated gene family in cancer. Der and Papke report in the review that despite decades of effort, drugs targeted against these gene mutations have not been developed. However, they also report that promising approaches are on the horizon.
“Much of what has stymied our past progress was an incomplete understanding of how RAS drives cancer development and growth,” said Der, a UNC Lineberger member and Kenan Distinguished Professor in the Department of Pharmacology at UNC-Chapel Hill. “It is now clear that the cancer cell is much more complex, and versatile, than we gave it credit for in the past. An important new lesson learned has been how resourceful a cancer cell can be when faced with a therapy; it has the remarkable ability to adapt to new therapies, rendering them ineffective. So, we hope we are smarter now and can keep one step ahead of the cancer and anticipate how it can adapt, and then block that adaptation.”
In the review, the UNC Lineberger researchers described several promising areas of research that have emerged due to new directions of research, novel ideas, and evolving technologies. A resurgent interest in RAS has stimulated researchers from other fields to bring fresh ideas and insights to the search.
Der said the most promising approach under investigation is the inhibition of signaling cascades that are stimulated by the mutant RAS gene in cancer.
“There are already inhibitors of these signaling cascades — in particular, protein kinase inhibitors — under clinical evaluation,” Der said. “What we now need to accomplish is to figure out the best combinations of drugs to make these signaling inhibitors more effective – less toxic to normal cells, and more potent in killing tumor cells.”
Der’s laboratory has studied RAS for more than three decades, but he is not alone at UNC. In collaboration with other groups at UNC, Der is working to bridge research areas, and bring powerful research tools to aid in the effort.
“Our lab and our UNC Lineberger collaborators are funded by several NCI team grants that support our studies,” he said.