Yvonne Vasquez
University of California Santa Cruz
Santa Cruz, CA
Comparative RNA sequencing analysis identifies therapeutic targets for children with difficult-to-treat cancers and leads to remarkable disease control in an ultra-rare tumor
Childhood cancer outcomes have improved over the past few decades, but patients with difficult-to-treat tumors still fare poorly. Tumor DNA profiling reveals therapeutic targets in few pediatric cancers because of their low rate of recurrent mutations. We hypothesized that analyzing tumor RNA in addition to DNA information would increase the number of actionable targets for pediatric cancers. We developed a Comparative Analysis of RNA Expression (CARE) approach to compare gene expression profiles of individual tumors to a large multi-institutional tumor cohort to identify overexpression outliers that may serve as potential therapeutic targets. We applied CARE to 33 Stanford Medicine Children’s Health patients with a recurrent/refractory or rare pediatric tumor who underwent tumor RNA and DNA sequencing. We compared each patient’s tumor RNA sequencing profile with over 11,000 uniformly analyzed tumor profiles. CARE revealed potential therapeutic targets for 31 of 33 (94%) patients, identified new treatments for 5 of 31 patients, and produced a clinical response in 3 of 5 patients treated with an identified therapy. In comparison, DNA mutations alone were potentially useful for treatment identification in only 15 of 28 (54%) tumors. In a remarkable case, CARE identified a targeted therapy for a child with myoepithelial carcinoma, an ultra-rare cancer for which no known effective therapies existed. The child is disease-free 18 months after taking the identified drug for two years. This study suggests that RNA analysis may identify additional druggable targets in patients with difficult-to-treat pediatric cancers relative to standard-of-care DNA profiling.
SACNAS National Diversity in STEM Conference, Portland, OR, October 26-28, 2023
