Gene Signature May Predict Response to Combination Therapy in Patients With NSCLC

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Researchers have identified a set of 140 genes that may help predict disease-free survival in patients with non–small cell lung cancer (NSCLC) treated with a combination of immunotherapy and low-dose radiation, according to a recent study published by Altorki et al in Cell Reports Medicine. The findings suggested that a gene signature of enhanced proliferation could be used to identify a subclass of lung tumors that is more likely to be eradicated by immunotherapy.


Lung cancer is the leading cause of cancer mortality in the United States and across the world. NSCLC accounts for 80% to 85% of all lung cancer cases.

Although immunotherapy may be an effective therapy in patients with NSCLC, only about 20% to 25% of them respond to this type of treatment. Prior research has uncovered that adding a low dose of radiation to a course of durvalumab may promote cancer-free survival in most patients with NSCLC.

Predicting who would benefit from immunotherapy and why could help patients who didn’t respond to treatments such as chemotherapy.

Study Methods and Results

In the recent study, researchers examined the pretreatment tumor biopsies of 60 patients with NSCLC to determine why some of the tumors didn’t respond to therapy. They determined the gene expression profiles that showed the specific genes that were turned up or down in each sample.

The researchers then compared the gene expression profiles of 10 tumors that reached major pathologic response with combination treatment with six tumors that didn’t reach major pathologic response. They discovered that the two groups of pretreatment tumors could be reliably distinguished by a set of genes—135 of which were turned up and 5 of which were turned down. They noted that the majority of the 135 genes were associated with enhanced cell growth, suggesting that the tumors that responded to the combination therapy were particularly aggressive.

They further examined how the gene expression profile changed in the tumors that responded to therapy pre- and posttreatment and revealed that in the tumors displaying major pathologic response, combination therapy not only reversed the activity of the 140-gene set, it also increased the activation of genes associated with immunity and tissue repair cellular pathways.


The researchers highlighted that the activity of the 140 genes that correlated with treatment responses may be used to distinguish patients who would benefit most from immunotherapy.

The researchers plan to conduct further studies with a larger group of patients analyzing whether tumors with this aggressive gene signature may have a better response to the combination therapy.

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