Abstract 4997: The ROSALIND Study: Identifying multi-omic signatures in long-term cancer survivors for therapeutic target discovery

Abstract Background: Long-term survival in cancers with poor prognosis, such as metastatic pancreatic ductal adenocarcinoma (mPDAC), glioblastoma (GBM-IDHwt), and extensive-stage small cell lung cancer (ES-SCLC), is exceedingly rare. The ROSALIND study is designed to explore the biological factors that contribute to exceptional survival in these cancers by comparing multi-omic and clinical profiles of long-term survivors (outliers) with those of patients who exhibit standard survival outcomes. By building a comprehensive clinical and molecular database, the study aims to identify novel therapeutic targets that could benefit a broader cancer population. Methods: ROSALIND is a retrospective, multi-center, case-control study conducted across three cohorts: mPDAC, GBM-IDHwt, and ES-SCLC. Cases (long-term survivors) are defined as patients with survival exceeding 5 years for mPDAC and ES-SCLC, and 3 years for GBM-IDHwt. Controls are matched to cases based notably on tumor stage, age, sample type and treatment history, with overall survival in the control group centered around the median overall survival reported in pivotal clinical trials for each tumor type. Tumor samples from over 500 long term survivors and matched controls are undergoing multi-omic analysis, including genomics, transcriptomics, proteomics, microbiomics and radiomics, with centralized sample processing at Gustave Roussy Cancer Campus / Paris Saclay Cancer Cluster. The molecular profiling pipeline includes 10X Visium HD spatial whole transcriptomics, whole-genome sequencing (WGS) or Whole-exome sequencing (WES), bulk RNA sequencing (RNAseq), microbiomics (16s rRNA) and proteomics. Results: As of October 2024, 135 patients have been enrolled in the ROSALIND study across three cohorts: 38 with ES-SCLC, 62 with GBM-IDHwt, and 35 with mPDAC. These patients were drawn from a global network of over 50 centers in 37 countries, and a total of 1211 outliers have been identified for potential inclusion. Molecular data collection is ongoing, with tumor and clinical data being curated into a centralized, multimodal database. The study aims to uncover key differences in molecular signatures between outliers and standard survivors, focusing on dysregulated pathways and proteins that may serve as novel therapeutic targets. Conclusions: The ROSALIND study is pioneering the creation of an extensive, multi-omic and multimodal database of cancer outliers worldwide and at scale. By examining at the spatial and single cell level the biological underpinnings of exceptional survival in some of the most aggressive cancers, this study holds the potential to discover novel therapeutic targets. Future findings from ROSALIND could lead to the development of precision oncology treatments aimed at replicating the biology of long-term survivors, thereby improving outcomes for patients with poor-prognosis cancers. Citation Format: Julieta Rodriguez, Olivia Le Saux, Paloma Cejas, David Gentien, Nick Riddiford, Naouel Zerrouk, Josep Tabernero, Olivier Elemento, Adrien Paix, Alexandre Yazigi, Nicolas Wolikow, Simon Istolainen, Remi Nicolle, Cécile Badoual, Elisabeth Auzias, Ludovic Lacroix, Nathalie Droin, Gina Dörpholz, Rodrigo Dienstmann, Jean-Yves Blay, Ulrich Keilhoz, Fabrice Andre. The ROSALIND Study: Identifying multi-omic signatures in long-term cancer survivors for therapeutic target discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4997.