Expression Levels of SMARCA4/BRG1 Gene Indicates Response to Chemotherapy
Significant sensitivity to cisplatin-based chemotherapy is signaled by the presence of low expression of SMARCA4/BRG1 in patients with earlier-stage non-small cell lung cancer (NSCLC). Low expression of SMARCA4/BRG1 was also linked to a poor prognosis.1
Our study suggests that SMARCA4, a gene commonly mutated in patients with NSCLC, might identify those patients who will benefit from treatment with cisplatin and other platinum-based drugs, explained Erica Hlavin Bell, PhD, assistant professor of radiation oncology at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in Columbus, Ohio, and first author of the study.
Lung cancer is the leading cause of cancer death. NSCLC accounts for 85% of lung cancers in the United States.
"Lung cancer is such a deadly disease because the majority of the cases are detected at advanced stages and because most patients harbor tumors that do not have targetable mutations," Bell said. "This leaves chemotherapy as the only therapeutic option after surgery, but there are few biomarkers to indicate which agents will benefit a particular patient.
The researchers found that patients with earlier-stage NSCLC whose tumors show low expression of SMARCA4 are likely to benefit from cisplatin-based chemotherapy compared with patients with high expression of the gene.
Furthermore, patients with tumors showing high SMARCA4 expression received no benefit from adjuvant chemotherapy compared with observation alone after surgery.
The researchers stated that, if their findings are confirmed, then patients with high expression of SMARCA4 should be spared the harsh effects of cisplatin, and treatment with an alternative therapy should be attempted sooner.
The study used an analysis of gene expression in 440 patients with NSCLC.
"Overall, the findings from this study might help us individualize chemotherapy treatment options in lung cancer patients after surgery," Bell concluded.
Funding from the Lung Cancer Research Foundation, the Paul P. Carbone Memorial Foundation, Lungevity, and the National Cancer Institute (grants CA108633 and CA148190) supported this research.
1. Bell EH, Chakraborty AR, Mo X, et al. SMARCA4/BRG1 Is a novel prognostic biomarker predictive of cisplatin-based chemotherapy outcomes in resected non-small cell lung cancer [published online ahead of print December 15, 2015]. Clin Cancer Res. doi:10.1158/1078-0432.CCR-15-1468.