Role of CCL2 and IL-8 in pituitary neuroendocrine tumor microenvironment

Pedro Marques, MD, PhD

Year: 2021
Institution: Centro Hospitalar Universitário Lisboa Norte EPE, Hospital de Santa Maria
Country: Portugal
Award Type: Pilot
NET Type: Other
Science Type: Translational


Hao will develop oncological positron emission tomography (PET) imaging probes to detect synaptic vesicle protein 2A (SV2A) in NETs. 

What question will you try to answer through your research?

There has been a growing realization about the nervous system’s role in the growth and spread of cancer, with some clinical trials showing that blocking nerve signaling could slow cancer progression. NETs arise from the cells of the nervous and endocrine systems, which gives NET cancer cells traits of both nerve cells (neurons) and hormone-producing endocrine cells. However, the influence of neurons on the formation and progression of NETs remains unclear due to the lack of an effective tool to target neuron-cancer interactions. I will work on developing a non-invasive PET imaging tool to explore new diagnosis and treatment options for NETs by targeting these interactions.  

Why is this important?

The role of the nervous system in the growth and spread of cancer has long been overlooked. Research studies have shown “crosstalk” between tumors, nerves, and the tumor environment, and other studies have linked tumor nerve density with aggressiveness and prognosis in some NETs. SV2A PET imaging probes are currently used to measure and evaluate neurodegenerative diseases, and we will develop its oncological version of the probes to investigate the neuron-cancer interactions in NETs outside of the brain. 

What will you do as part of this research project?

We will measure and compare the expression of SV2A and other common NET biomarkers in a series of NET cell lines and tumors. We will develop new PET probes for SV2A in NETs to focus on improving the tumor localization and imaging. 

How might your research improve the treatment of NETs?

We expect that the new SV2A imaging tool will advance our knowledge of the role of the nervous system in NETs. The imaging tool may be used to screen NET patients to potentially start treatments earlier for better outcomes. It could also lead to new treatment options for NETs that can therapeutically target the interactions between neurons and cancer cells.

What is your next step?

As a pilot study, our project explores the ability to detect NET tumors by PET imaging of SV2A with newly developed probes. If the new imaging probes are promising, radionuclide therapy could be used to target SV2A in NETs. Also, the SV2A PET imaging may lead to a preclinical study of new treatment options that act on the interaction between neurons and cancer cells.