Oesophageal Cancer Clinical and Molecular Stratification
MRC Cancer Unit, Cambridge
Esophageal cancer is an area of unmet clinical need; the majority of patients present with advanced disease. OCCAMS (Oesophageal Cancer Clinical and Molecular Stratification) is an established UK wide network recruiting patients diagnosed with esophageal adenocarcinoma (EAC) including tumours of Gastro-oesophageal Junction (GOJ). They have accrued clinical data and samples from over 4,000 patients, to attempt to identify clinical, demographic and molecular factors affecting disease progression. This cancer is dominated by copy number changes and structural variation; therefore whole genome analyses are required. Profiling more cases of EAC with integrated clinical-pathological and multiomic datasets will enable us to identify predictors of response to therapy. They will use WGS coupled with RNAseq where possible to uncover new causative variants. Alongside this, OCCAMS will assess data from clinical trials, including a study currently in the design phase, which aims to determine if FDG-PET and ctDNA can predict response to chemotherapy in EAC patients.
Project Goals and Expected Outcomes
Survival statistics for Esophageal adenocarcinoma (EAC) are dismal. It is the fastest-rising cancer in the developed world. The majority (60%) of patients present with advanced disease and most patients who are treated with partial remove of the esophagus or with oncological therapy do not benefit. OCCAMS is an established network of clinical centres recruiting EAC patients for tissue collection. EAC patient data and tissue samples are used to attempt to identify factors affecting disease progression. This will allow us to make better treatment decisions for patients, to tailor their therapies based on their individual tumour.
What gaps in existing knowledge will be addressed by the study?
For esophageal adenocarcinoma the application of molecular targeted therapies has lagged behind other cancers and recent trial data have been disappointing. Currently the only licensed molecular targeted drug for esophago-gastric adenocarcinoma is Trastuzumab targeting HER2, which is licensed in the metastatic setting. Furthermore, accumulating evidence suggests that intra-tumoral heterogeneity and receptor tyrosine kinase co-amplification significantly attenuates the response to targeted therapy for a range of RTK inhibitors including HER2. This study aims to identify clinico-pathological and molecular predictors of response and targets for therapy.
Rebecca Fitzgerald, MD, FRCP, FMedSci
European Bioinformatics Institute (EMBL-EBI)
University of Southampton
Cambridge University Hospitals NHS Trust
University of Southampton