About A.L.B. (Ann) Seyhaeve, Assistant Professor
Introduction
A tumor does not solely exist of tumor cells. The tumor microenvironment is equally important to contribute to tumor growth and development and has therefore also an significant role in treatment. It is important to better understand the connection between cells of the microenvironment (e.g. endothelial cells, pericytes, fibroblast, immune cells,…) and tumor cells to develop more efficient therapies. However, the relationship between microenvironmental cells, therapies and other diseases is never far away resulting in spin-off investigations.
Investigating the Tumor-associated Vasculature
Especially the tumor-associated vasculature has an important role to fulfill as this brings nutrients and oxygen to the tumor and removes toxic compounds. However, the vasculature is also the route into a tumor when systemic chemotherapy is administered. We are investigating how we can improve intratumoral drug delivery by manipulating specifically the tumor-associated vasculature. Tumor vessels exist predominantly of endothelial cells, that form a barrier between blood and underlying tissue and, of pericytes that wrap around the endothelial tube creating support of a blood vessels. There is little know regarding these pericytes and we are investigating the association between endothelial cells, pericytes and tumor cells.
Investigating Tumor Immune Invasion
Also tumor infiltrating immune cells are important in the development and treatment of tumors. Especially melanoma cells can hijack signaling pathways to evade antitumor immunity and contributes to resistance of immune therapy. We are investigating the Melanocortin-1 receptor (MC1R) signaling pathway. Hypothetically, there is a protective role of MC1R against melanoma when afamelanotide, a α-Melanocyte-Stimulating Hormone that binds to MC1R, is administered. However, the role of MC1R and afamelanotide treatment once a melanoma tumor is established and the possibility that the tumor take over this pathway to support tumor progression is less studied and we are exploring this connection.
Investigating Erythropoietic Protoporphyria
Afamelanotide stimulates production of melanin (= tanning) in the skin without the need for sunlight. This compound is administered to patients with erythropoietic protoporphyria (EPP), a rare disease making patients extremely sensitive to light. This chemical induced tanning prevents penetration of sun light into their skin that otherwise would cause damage, blistering and pain. As afamelanotide is registered as an orphan drug there is little know regarding the exact mechanism as well as the exact genetic route and biological consequences of the disease itself. We are investigating the role of afamelanotide in the management of EPP and also the relation between several genes with clinical EPP manifestation.
