Mutations are Not All the Same

Dr. Lenz

We are making significant progress in understanding what genetic alterations in tumors really mean.

Over the last two years, we have learned or the first time that there is an alteration in a gene called KRAS in colon cancer, and tumors which have this mutation do not respond to treatment with Erbitux® (cetuximab) or Vectibix® (panitumumab).

This is the first time we have a marker to test for sensitivity of an antibody we have to treat colon cancer.

It is very important to know that patients with tumors who carry a KRAS mutation (alteration) are not doing worse overall. They just don’t have any benefit from an antibody which targets the Epithelial Growth Factor Receptor (EGFR).

Only a few weeks ago, an international group showed for the first time that the different mutations we see in KRAS are not all the same. A mutation is usually a change in one spot (exon) on the gene, but it may happen at many different locations in the gene. The effect may be different depending on the location where it occurs.

Most of the KRAS mutations are in two areas, exon 12 and exon 13. Depending on their location these changes will have different impact on the protein function, and, therefore, maybe all will not  predict resistance to Erbitux.

The investigators have preliminary data that patients with tumor mutations in exon 13 may benefit from Erbitux. These are important findings and in the future may mean that patients with KRAS mutations in exon 13 may receive Erbitux therapy.

In my practice I am making sure that I identify all these patients, who are up to 20% of all patients with KRAS mutations. In the next couple of months, we will have more information which will give us a more conclusive answer.