Inhibition of Epithelial to Mesenchymal Transition (EMT) for Treatment of kidney Cancer (expansion of project 8675)

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Kidney cancer is a common cancer in human. There is a lack of options for therapy of kidney cancer in advanced disease and a need for targeted therapies to improve outcome. In the European Union, around 35,000 renal cancer deaths occurred in 2012. In Norway, there were 814 new cases of kidney cancer reported in 2014. Clear cell renal cell carcinoma (ccRCC) represents the most common (75-85%) form of renal cancer and the most lethal genitourinary cancer. Up to a quarter of patients display metastases or advanced regional disease at the time of presentation.

EMT is a process by which epithelial cells change into cells with mesenchymal characteristics that can locally invade and migrate. EMT plays an important role in the development, growth and spread of kidney cancer and as well as modulation of associated stroma and fibroblasts. Axl is a central pathway/receptor involved in EMT.

In this project, we hypothesize that Axl inhibition can inhibit the growth of renal clear cell carcinomas by inhibiting EMT, and consequently disrupting the interaction with the cancer associated fibroblasts. And we aim to explore the effect of four Axl signalling inhibitors in the development and progression of kidney cancer.

This project will help to elucidate both the impact of EMT, cancer associated fibroblasts and Axl in kidney cancer but also analyze the potential treatment of kidney cancer with these Axl-inhibitors.

We suggest to use 960 mice (240 PALB/C NUDE, 240 NOD/SCID and 480 C57BL/6). Severity of the animals distress is to be classified as mild to moderate depending on the model used.