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Project
Identifying and targeting the support of never healing wounds, cancer associated fibroblasts in liver tumors (FWOAL1011)
Chronic liver disease results in fibrosis, thereby creating a suitable
environment in which primary liver tumors develop. Furthermore, the
liver is an important site for metastasis of other tumors such as colon,
breast, lung and melanoma cancer. In both cases, patients have a
poor prognosis and liver cancer is associated with high mortality.
Most anti- liver cancer treatments focus on the rapidly dividing and
evolving cancer cells, unfortunately unsuccessfully. In this project we
will use an innovative approach to investigate the cells in the tumor
environment that support tumor growth. This cancer associated
fibroblasts, have many characteristics of liver resident stellate cells.
Stellate cells are in a healthy liver involved in vitamin A storage and
control the amounts of connective tissue in the organ. Upon liver
injury, stellate cells activate and become scar producing
myofibroblastic cells. Because of the phenotypic overlap between
cancer associated fibroblasts and stellate cells, we will compare
these cell types more in depth. We would define if cancer associated
fibroblasts are a homogeneous population that could be
therapeutically targeted or whether different cancer associated
fibroblast-types exist with different roles in tumor support and in that
case, targeting subtypes would be beneficial. We will use a strategy
described for stellate cells to deliver drugs to cancer associated
fibroblast and evaluate the impact on tumor growth.
environment in which primary liver tumors develop. Furthermore, the
liver is an important site for metastasis of other tumors such as colon,
breast, lung and melanoma cancer. In both cases, patients have a
poor prognosis and liver cancer is associated with high mortality.
Most anti- liver cancer treatments focus on the rapidly dividing and
evolving cancer cells, unfortunately unsuccessfully. In this project we
will use an innovative approach to investigate the cells in the tumor
environment that support tumor growth. This cancer associated
fibroblasts, have many characteristics of liver resident stellate cells.
Stellate cells are in a healthy liver involved in vitamin A storage and
control the amounts of connective tissue in the organ. Upon liver
injury, stellate cells activate and become scar producing
myofibroblastic cells. Because of the phenotypic overlap between
cancer associated fibroblasts and stellate cells, we will compare
these cell types more in depth. We would define if cancer associated
fibroblasts are a homogeneous population that could be
therapeutically targeted or whether different cancer associated
fibroblast-types exist with different roles in tumor support and in that
case, targeting subtypes would be beneficial. We will use a strategy
described for stellate cells to deliver drugs to cancer associated
fibroblast and evaluate the impact on tumor growth.
Date:1 Jan 2021 → 31 Dec 2022
Keywords:Primary and secondary liver cancer, Liver fibrosis, Cancer associated fibroblasts
Disciplines:Cellular interactions and extracellular matrix, Hepatology (incl. pancreas), Cell signalling, Cell growth and development