Since the discovery of the first human oncogene, KRAS, in the early 1980s there has been an explosion in our understanding of cancer. Drugs targeting other oncogenes such as the protein kinase BCR-ABL which causes a type of blood cancer have profoundly affected the lives of cancer patients since the approval of imatinib in 1999. While the pace of discovery of drugs which target certain classes of oncoproteins (protein kinases in EGFR driven lung cancer and nuclear hormone receptors in breast and prostate cancer) have been remarkable, the cancers driven by the GTPase, KRAS, have been slower to develop because the K-Ras protein lacked obvious drug binding pockets. I will discuss the challenges faced by academic and industry scientists which led to the notion that K-Ras was “undruggable”.

In 2013 our laboratory reported the first drug binding pocket on K-Ras (G12C) which was followed eight years later by the FDA approval of sotorasib and adagrasib. The current challenge of developing drugs for other even more common K-Ras mutants such as K-Ras (G12D) will be discussed including current agents in clinical trials as well as how to leverage the immune system to further attack K-Ras mutant driven lung, colon and pancreatic cancer.

Camille & Henry Dreyfus Lectureship
In memory of the Dreyfus brothers, the Camille and Henry Dreyfus Foundation Inc. has established the Camille & Henry Dreyfus Lectureship at the University of Basel. The annual Lectureship brings a leading chemist from the United States to the Basel campus to deliver a series of talks, and to meet with faculty and students in order to enhance the relationship between Swiss and U.S. science.