Breast Cancer Metastasis Research Group

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. About half of patients with CRC develop liver metastases, and many ultimately succumb to their disease. At the histopathological level, colorectal cancer liver metastases can be grouped into two major histological growth patterns (HGPs): replacement-type (rHGP) and encapsulated (eHGP). These growth patterns have strong prognostic significance, with patients developing encapsulated lesions exhibiting superior overall survival.

In encapsulated lesions, cancer cells are separated from the surrounding liver tissue by a fibrotic rim and depend heavily on angiogenesis for vascularization. In contrast, replacement-type lesions grow in direct contact with hepatocytes and hijack the liver’s existing sinusoidal blood vessels. Preliminary work in our lab suggests that these two lesion types do not differ significantly in their mutational profiles, pointing to alternative mechanisms that drive these distinct HGPs. Based on known differences in transcriptional profiles between encapsulated and replacement-type CRC liver metastases, we believe that epigenetic changes may contribute to the formation of these two HGPs. My project uses patient-derived xenograft (PDX) models developed in our lab to explore the epigenetic landscapes of replacement- and encapsulated-type CRC liver metastases.