In a recent study, the researchers looked at the RNA in renal cell carcinoma (RCC) tissue samples from patients being treated with immune checkpoint inhibitors (e.g. nivolumab, pembrolizumab, avelumab) to try to identify a biomarker for response to treatment. They found that patients with low levels of a protein-coding gene called PARP1 (poly (ADP-ribose) polymerase 1) who were treated with the PD-1 inhibitor nivolumab had much better survival.
These survival benefits were even more pronounced in patients who had RCC tumours with a mutation in the protein-coding gene, PBRM1 (polybromo 1). These survival benefits in patients with low levels of PARP1 were not seen in patients who were treated with everolimus.
These results suggest that PARP1 could be used as a biomarker to predict response to immune checkpoint inhibitors in patients with clear cell RCC. Ongoing clinical trials are also looking at the effect of combining immune checkpoint inhibitors with PARP1 inhibitors for the treatment of advanced clear cell RCC.