When Gleevec, the very first targeted therapeutic came out, there was a mad rush in the pharmaceutical industry to mine the genome for potential “magic bullet” targets. In Gleevec’s case, it was able to inhibit the BCR-ABL fusion kinase, and turn a deadly disease into a manageable chronic condition. But with a disease as complex as pancreatic cancer, the prospect of finding a “magic bullet” target seemed remote.
This week however, scientists at the University of Michigan (publishing in the Journal of Clinical Investigation) were able to demonstrate that by inhibiting the gene KRAS in a mouse model, precancerous lesions and tumors could be destroyed. KRAS plays a critical role in the early stages of pancreatic cancer (as shown in the KEGG pathway diagram below) and this study demonstrates that KRAS could make a very promising drug discovery target.
As anyone in the pharmaceutical industry will tell you though, there’s a lot of work between identifying a promising target, and having a drug ready for clinical trials. But this is a promising start to validating KRAS as a potential target.