Defining the Origin, Evolution and Therapeutic Vulnerabilities of Metaplastic Colorectal Cancer

ASPIRE Award (2023-Present)

Owen Sansom, PhD, Cancer Research UK Beatson Institute

Owen Sansom, PhD

Although the genetic drivers underlying colorectal cancer (CRC) have been studied for decades, the current molecular models of the disease have not translated into improved outcomes for most patients. Recent advancements in transcriptional profiling techniques have allowed researchers to identify a previously unrecognized CRC subtype that constitutes a significant proportion of CRC cases. This subtype, which constitutes over 50% of CRC lesions, is associated with chronic inflammation that defines the transcriptional and epigenetic outcome of the tumor.

Now, Owen Sansom is leading a project to model and characterize this CRC subtype. This will be done using preclinical mouse models and integrating the findings with clinical studies to gain insights into tumor initiation, evolution, metastasis, and therapeutic response. Owen and his team will determine whether current preclinical models accurately represent this class of CRC and uncover the main drivers behind tumor initiation and maintenance in this subtype. By addressing these questions and integrating insights from preclinical models and clinical studies, the project aims to de-risk future large-scale therapeutic intervention programs for this subtype of CRC, potentially leading to significant advancements in the clinical management and treatment of the disease.