Small cell lung cancer (SCLC) tumors that harbor no mutation in RB1 may have a poor response to chemotherapy, according to a study published in Annals of Oncology.

Researchers led by Afshin Dowlati, MD, of Case Western Reserve University in Cleveland, OH, looked at 50 patients with SCLC, using targeted exome sequencing on 42 of them and whole-exome sequencing on 8 in order to correlate mutations with main clinical outcomes of response to chemotherapy as well as progression-free and overall survival.

In total, they found that 389 patients had extensive stage-SCLC, with 15 who had either primary refractory/resistant disease, and 21 who had sensitive disease. The 2 most frequently mutated genes were found to be TP53 (86%) and RB1 (58%).

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Upon multivariate analysis, they found that RB1 was the only significant factor in predicting response to first-line chemotherapy, with an odds ratio of 5.58 comparing mutant RB1 to wild-type.

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Patients with mutant RB1 were found to have both better overall and progression-free survival compared to those with wild-type RB1.

“Interestingly, about 25% of SCLC cell lines and tumor specimens expressed RB1 protein, possibly representing the subgroup with wild-type RB1,” the authors noted.


  1. Dowlati A, Lipka MB, McColl K, et al. Clinical correlation of extensive-stage small cell lung cancer genomics [published online ahead of print January 22, 2016]. Ann Oncol. doi: 10.1093/annonc/mdw005.