Defining the immune landscape of NETs – towards rational combination therapy

Tim Meyer, MD, PhD

Year: 2015
Institution: University College London
Country: United Kingdom
Award Type: NETRF GRANTS 2005-2017
NET Type: Gastrointestinal
Science Type: Translational

What question will scientists try to answer?

Can we develop laboratory models of neuroendocrine tumors (NETs) to use in large-scale drug screens that may identify the rare anti-tumor agents that can effectively treat human NETs, in particular, the deadly NETs that often metastasize?

Why is this important?

It is critical to develop laboratory models of NETs in order to test the large numbers of compounds needed to find the few possessing good anti-tumor activity. Regrettably, non-human models of cancer often fail to fully recapitulate the human disease and many anti-cancer drugs that were effective in the laboratory failed to work as well in human patients. Thus, it may be more effective if cancer therapeutics were screened using human cell NET models. Unfortunately, there are very few reliable patient-derived NET cell lines that researchers can use to test drugs, so Dr. Ear has developed a novel strategy to circumvent the lack of these cell lines for her large-scale drug screens.

What will scientists do?

Dr. Ear has developed a way to isolate small-bowel NET cells directly from resected patient tumors and grow them in the laboratory as small clusters of cells called “spheroids.” She can grow these clusters in large enough numbers to be used to screen the anti-tumor properties of hundreds of potential therapeutic compounds.

Furthermore, she also proposes to inject these spheroids directly into the spleen of a strain of mice that will allow human tumor cells to survive and metastasize to the liver, as it often does in human patients. Because these NET spheroids are human cells, she can use the same NET-imaging agent used in humans (Ga-68 dototoc) in order to track and analyze their metastasis by PET scan in the living animals. She can then further test the effectiveness of anti-tumor drugs identified in her initial studies using this live metastasis animal model.

How might this improve treatment of NETs?

Dr. Ear’s work has the potential to move us closer to establishing a reliable laboratory disease model that researchers can use to study the process of NET metastasis and to test, and identify, new and different drugs for therapeutic development.

What is the next step?

If successful, she will publish her results and make her cell or mouse models available to the scientific community to further our understanding of NET biology, NET metastasis and to uncover future therapeutic options for the treatment of NET patients.