A signature for success

Abstract

The expression pattern of 13 genes can predict whether cancer cells will be sensitive to drugs that inhibit a protein that represses the activity of p53.

Keywords: human; human biology; medicine; p53; predictive signature; translational oncology.

Figure 1.. A gene expression signature predicts the response of cells to drug treatments that inhibit MDM2.

The tumor suppressor protein p53 promotes cell death and halts cell division by activating an enzyme called RNA polymerase II (RNAPII) to drive the expression of particular genes. However, in many cancer cells, p53 is deactivated by another protein called MDM2 (left). Jeay et al. report that a “signature” formed by the expression levels of 13 genes can predict whether or not cancer cells will respond to two drugs -- NVP-CFC218 and NVP-CGM097 (denoted by a red star) -- that inhibit the activity of MDM2. The signature predicted that 27 of the 55 tumor samples collected from patients would be sensitive to the drugs, and 19 of the 27 tumors decreased in size after treatment (top). The 13 genes in the signature are all regulated by p53, which suggests that there is least some ‘leaky’ p53 activity (indicated by the dotted line) in the cells of sensitive tumors before the drug treatment (top left). The other 36 tumor samples—most of which lacked the gene signature—continued to grow after the drug treatment (bottom), although the reasons for this are not fully understood.