Scientists at Fox Chase Cancer Center have identified a mutation in the KRAS oncogene that may play a significant role in colon cancer. This discovery could lead to “ultrapersonalized” treatments, targeting specific gene mutations in patients.
“The implication is that if you are a person with this particular type of KRAS mutation — which is not rare — then you might benefit from a particular combination of therapies that would not work if you had another type of KRAS mutation,” said Chernoff, an oncologist and Cancer Center Director at Fox Chase. Chernoff was the senior author on the study.
KRAS mutations are common in colorectal cancer and are linked to poor prognosis and treatment resistance. Recent research indicates that different KRAS mutations may have unique properties.
In their study, researchers used CRISPR technology to create mouse colon cells identical except for the KRAS mutation they contained. They found one mutation, KRAS G12V, synthesized acetyl-CoA differently using a distinct enzyme.
“Acetyl-CoA is like a Lego brick — the ultimate one — because you can make a lot of things out of it,” Chernoff explained. Blocking the enzyme used by KRAS G12V could prevent acetyl-CoA synthesis, offering a new therapeutic target.
Researchers demonstrated this sensitivity in cell lines and mice experiments. “This offers the first really direct attack on this particular type of mutation,” Chernoff stated.
Future studies will test these findings in human models of colon cancer and explore similar studies in pancreatic and lung cancers where KRAS mutations are prevalent.
The paper was published in Cell Reports.
