For oncologists specializing in renal cell carcinoma (RCC), their enthusiasm about the recent approval of 4 immunotherapies has been tempered by frustration. That’s because it’s unclear why only a minority of patients respond favorably to them. In an attempt to shed light on the mystery, researchers have spent the last decade hunting for molecular biomarkers that might reveal who may be ideal candidates to receive such therapies.

So far, the search has been disappointing. In fact, a new review by an Italian team at the University Hospital of Parma and published October 2019 in Expert Review of Molecular Diagnostics concluded that researchers aren’t any closer to an answer. The team surveyed the current literature from 2010 through 2019 on the most studied biomarker in blood and tumor tissue in patients with metastatic RCC who had been treated with immune checkpoint inhibitors, and found that the expression of PD-L1 alone did not predict whether the drug worked.

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“The treatment landscape of metastatic RCC has dramatically changed in the last years, and we wanted to identify molecular biomarkers which could be a useful tool to avoid choosing an ineffective therapy in patients who might suffer from unnecessary side effects and financial burden,” said lead study author and medical oncology resident Sara Elena Rebuzzi, MD.

She says her team’s study is important because it encourages researchers to broaden their focus by looking at “proangiogenic or proimmunogenic genomic and transcriptomic signatures” in tumor microenvironments. “We need to look at combinations of biomarkers rather than a single biomarker,” said Dr Rebuzzi.