Functional characterisation of Transient Receptor Potential Vanilloid (TRPV2) as a potential new target for endometrial cancer

Endometrial cancer is the fourth most common type of female cancer with a poorer prognosis and high risk of metastasis. Increasing evidence demonstrates that the Transient Receptor Potential Vanilloid 2 (TRPV2) exhibits oncogenic activity in endometrial cancers. Functional TRPV2 expression is linked to mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT), providing strong evidence for a potential role of TRPV2 in cell proliferation and migration. Therefore, TRPV2 represents a new therapeutic target in cancer treatment. Thus, it prompts the pharmacological use of TRPV2 targeting in the control of cancer progression. Unfortunately, the existing pharmacology of TRPV2 is very sparse and mostly nonspecific. In this project, I intend to explore natural sources such as animal venoms and plant extracts for potent and selective TRPV2 ligands that will be used as valuable tools to aid in studying the TRPV2 channel. Moreover, I aim at a detailed structure-function analysis to obtain an in-depth biophysical characterisation of the TRPV2 channel. Finally, to validate the anti-tumour properties of TRPV2 targeting compounds, I will use endometrial tumour cell lines with a variable EMT status and patient-derived endometrial cancer organoids to investigate TRPV2 as a target for the treatment of endometrial cancer. The outcome of this project will shed light on whether TRPV2 represent a valuable pharmacological target for drug design to treat endometrial cancer.