Spatial profiling of gastric cancer with peritoneal carcinomatosis to tackle cancer spreading and improve precision immuno-oncology

forthcoming

The SPARC project tackles the urgent challenge of poorly cohesive gastric cancer (PCGC) with peritoneal carcinomatosis — an aggressive malignancy associated with a 5-year survival rate <30%. Despite advancements in GC treatment, effective therapies for PCGC with peritoneal spread remain inadequate, largely due to the tumor’s resistance to chemotherapy and the complex tumor microenvironment. This microenvironment is involved in hijacking cancer immune surveillance and supporting tumour outgrowth and invasion. However, the detailed molecular and spatial dynamics promoting PCGC dissemination are not yet fully understood. The project aims to fill this gap and elucidate the molecular and cellular mechanisms driving this aggressive behavior by employing advanced spatial immunofluorescence (IF) imaging and spatial transcriptomics to map the tumor and immune microenvironment of PCGC with synchronous peritoneal metastases, leveraging a rare biobank of treatment-naïve PCGC samples. This will enable to better understand the complex cellular interactions that drive tumor growth, immune evasion, and metastasis, as well as identify and validate - at both protein and gene expression levels - novel biomarkers specifically associated with peritoneal metastasis, serving as potential therapeutic and prognostic targets for this challenging cancer subtype. The project leverages an interdisciplinary collaboration between leading research institutions – Karolinska Institutet (Sweden, host institution), Yale University (USA, secondment institution), University Hospital of Verona (Italy, collaboration partner) – and is supported by renowned experts in immuno-oncology and GC that will provide multidisciplinary training to the researcher, enhancing their career prospects while addressing a significant unmet medical need.