Drug profiling for Hepatic Artery Infusion (HAI) therapy for neuroendocrine tumor liver metastases using patient-derived preclinical models

Many people with neuroendocrine tumors (NETs) develop cancer spread to the liver. While treatments exist, most slow tumor growth rather than shrink tumors, and liver-directed options often provide only temporary benefit. As a result, patients with liver-dominant NETs have limited long-term treatment choices if surgery is not feasible.

This project studies a treatment called hepatic artery infusion pump (HAIP) therapy, which delivers chemotherapy directly to the liver. HAIP is effective for other cancers that spread to the liver but has not been properly studied in NETs. Using tumor samples donated by patients, we will test which drugs work best when delivered this way and whether combining them with current NET treatments improves effectiveness.

Our goal is to generate the scientific evidence needed to design future clinical trials. Ultimately, this research aims to expand treatment options and improve outcomes and quality of life for people living with NETs and liver metastases.

Clinical Validation of an SSTR2-Targeted Liquid Biopsy for Circulating Tumor Cells in Well-Differentiated Pancreatic and Ileal Neuroendocrine Tumors.

Neuroendocrine tumors (NETs) are difficult to monitor because they often grow slowly, behave unpredictably, and may not cause symptoms for long periods. Doctors rely on specialized scans, such as DOTATATE PET imaging, to see where tumours are and how active they may be. While these scans are essential, they only provide information at one point in time. As a result, patients and their care teams may not know early enough whether treatment is working or if the cancer is changing.

Our team which consists of an expert in NETs and a clinical fellow who will be doing the work, aiming to develop a new blood test, called a liquid biopsy, that detects NET tumour cells circulating in the bloodstream. These circulating tumour cells (CTCs) can reveal important details about how the cancer is behaving throughout the body. Older CTC tests did not work well for NETs because they used markers that NET cells do not reliably express. To solve this, we created a NET-specific method based on SSTR2, the same receptor used for NET imaging and radioligand therapy. Using a fluorescent probe that binds to SSTR2, along with advanced tools that isolate and visualize single cells, we can detect NET CTCs with much greater accuracy.

This research aims to lead to a blood test that tracks NET progression. This test may help identify sooner whether treatment is effective, whether resistance is emerging, or whether the disease is returning, ultimately improving care and outcomes for people living with NETs.

A population-based evaluation of extra-hepatic GEP-NET metastases identified by 68Ga-DOTATATE PET/CT

Gastroenteropancreatic neuroendocrine tumours (GEP-NETS) frequently present with metastatic disease (spread beyond the primary tumour) at time of diagnosis. The most common sites of metastasis are local lymph nodes and liver, while other sites of metastasis were previously thought to be rare. However, traditional imaging has been limited by the small size of these metastases.

GEP-NETS have special receptors that bind an injectable tracer that lights up on imaging, such as the 111ln-Octreotide or the 68Gallium-DOTATATE PET/CT scan (68Ga-DOTA).

The 68Ga-DOTA scan has started to replace Octreotide scans due to faster imaging times, lower costs, and better ability to detect small tumours and metastasis. However, it still remains less readily available across Canada. Recent publications have shown that 68Ga-DOTA revealed 25 to 36% of patients have metastasis outside of the regional lymph nodes and liver, which is significantly higher than previously reported. Other studies have shown that 68Ga-DOTA leads to change in management in up to 56% of patients.

Our study aims to review the rates and locations of metastatic disease in Canadian patients with GEP-NETS that have undergone 68Ga-DOTA and compare this to cross-sectional imaging to see if there is a change in staging and management based on this information.

Investigating Lung Neuroendocrine Tumours Through the Canadian National CARMA-BROS Platform: Real-World Outcomes and Health Equity Advocacy

Neuroendocrine tumours (NETs) of the lung are rare cancers that range from slow-growing atypical carcinoid tumours to more aggressive large cell neuroendocrine cancers. Because these cancers are uncommon, there is limited information about how often they occur in Canada, and treatments are often adapted from other cancers, rather than being based on evidence specific to lung NETs.

This project will use a national Canadian research platform (CARMA-BROS) to collect real-world information on patients with lung NETs across the country. By examining management and outcome patterns, the study aims to identify gaps in care and regional differences in access to diagnostic testing, therapies, and clinical trials.

The study findings will support educational and advocacy initiatives as well as policy development to improve care for Canadians living with lung neuroendocrine tumours.

High-Resolution Methylation and Genomic Profiling of Small Intestinal Neuroendocrine Tumors Using Oxford Nanopore Sequencing

Well-differentiated small intestinal neuroendocrine tumors (WD SINETs) are a type of cancer that starts in the small intestine. They are the most common small bowel cancer but are difficult to manage because they do not all behave the same way. Pathologists currently grade these tumours based on how many cells are actively dividing, measured by a marker called Ki-67. Tumours with very low Ki-67 are usually slow growing (grade 1), and those with very high Ki-67 are aggressive (grade 3). However, grade 2 tumours, which fall into the broader middle range (3–20%), are unpredictable. Some behave indolently, while others progress quickly. This uncertainty makes it difficult for treating physicians to decide whether a patient should be closely monitored or start more active treatments earlier.

We believe that looking beyond Ki-67 to study changes in DNA may provide better answers. We will study DNA methylation, chemical marks on DNA that control how genes are switched on or off. Unlike older methods, which only capture a portion of these signals, we will use Oxford Nanopore sequencing technology to directly read DNA methylation, at a higher resolution, along with other important genetic changes in the same sample.

By studying 50 SINET tumours, we aim to uncover new DNA signatures that separate aggressive from less aggressive tumours, especially within grade 2. This information could lead to new diagnostic tools that help physicians predict how a patient’s cancer will behave and tailor treatment and monitoring more precisely.