ROR1 mRNA expression in EGFR-mutant non-small-cell lung cancer (NSCLC) patients (p) with the T790M mutation: A potential therapeutic target.

11027 Background: Progression-free survival (PFS) is short in NSCLC driven by EGFR mutations treated with erlotinib alone, due to crosstalk with other signaling pathways that can cause secondary dependency. ROR1 knockdown inhibited the growth of NCI-H1975 cells (with EGFR L858R and T790M mutations). A pro-survival function for ROR1/MEK/ERK signaling has been demonstrated, with cooperation with AKT. In a subset of 95 p in the EURTAC trial (clinicaltrials.gov NCT00446225), 65% had pre-treatment T790M mutations. We have assessed ROR1 expression in 45 of these 95 p. Methods: The T790M mutation was determined by Taqman with a PNA to inhibit amplification of the wild-type (wt) allele. Tumor samples were run in octuplicates; this method can detect 1 mutated allele among 10,000 wt alleles. ROR1 mRNA expression was examined by quantitative RT-PCR and categorized by terciles. p were classified as having low/intermediate or high ROR1 expression. The impact of ROR1 expression on outcome was examined in all 45 p and i...