Research project

Upfront locoregional surgery compared to delayed symptom-based surgery among initially asymptomatic patients with unresectable metastatic midgut neuroendocrine tumours

Neuroendocrine tumors (NET) represent a unique subset of malignancies. They have low mutational burden associated with slow growth and prolonged survival, even in the metastatic setting. Prior research has shown that those who achieve resection of primary tumor and debulking of 70-90% of liver tumor burden have improved survival.

However, the effect of upfront prophylactic bowel surgery on asymptomatic patients with liver metastases not amenable to debulking is contested. Prior research on this subject has produced mixed findings, and there are no randomized trials to guide clinical practice.

Our study seeks to characterize the management of asymptomatic midgut NET patients with liver metastases not amenable to debulking in southern Alberta. We designed a retrospective, population-based cohort study which leverages data from the large cohort of patients treated by the multidisciplinary NET tumor group at the University of Calgary over the last 25 years.

Patients will be identified from the Alberta Cancer Registry (ACR), and data relating to clinical, tumor, and treatment characteristics will be extracted from synoptic operative reports and individual review of electronic medical records.

The primary outcome is need for unplanned acute care admission and subsequent emergent and elective surgical interventions. Secondary outcomes include overall survival, progression free survival, admissions for complications related to their NET, and differences in surgical and non-surgical treatments between those who have upfront surgery compared to those who have delayed or no surgery.

We expect our findings to contribute to national and international guidelines on management of metastatic midgut NET.

Research project

High-resolution profiling of pancreatic neuroendocrine tumour heterogeneity and progression mechanisms

Pancreatic neuroendocrine tumours (PanNETs) are among the fastest-growing and deadliest types of neuroendocrine neoplasms with unpredictable clinical behaviour, driven by a subset of tumour cells that become more aggressive.

My project investigates the mechanisms behind this shift using high-resolution methods and clinically diverse PanNET patient samples.

I have identified a potential role for cell surface structures called cilia in driving PanNET progression, and will further explore how they regulate tumour behaviour.

This is the largest study of its kind to date and is expected to uncover novel prognostic or therapeutic targets, ultimately improving care for patients with this dire disease.

Research project

Integrating Long-Read Sequencing and Multi-Omic Profiling to Advance Precision Oncology in Gastroenteropancreatic Neuroendocrine Neoplasms

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are an uncommon group of cancers with limited treatment options. Although advances in genetic testing have improved our understanding of these tumours, current methods often fail to identify the biological changes driving their growth and behaviour. This makes it difficult to predict which patients are most likely to benefit from available and emerging treatments.

Our recent research showed that targeted genetic testing detects potentially clinically actionable changes in only a minority of GEP-NENs, suggesting that key features of these cancers are being missed.

This project will investigate whether a new technology called long-read sequencing can provide a more complete picture of tumour biology. Unlike conventional methods, long-read sequencing can examine much larger fragments of DNA and identify important genetic and gene-regulating changes that are difficult to detect using current approaches.

Using tumour samples from patients with advanced GEP-NENs enrolled through the BC Cancer Personalized OncoGenomics program, we will combine long-read sequencing with other more routine molecular sequencing technologies and clinical information. This will allow us to determine whether hidden biological features of these tumours are linked to how they behave and respond to treatment.

To our knowledge, this will be the first study to apply long-read sequencing to GEP-NENs. By improving our understanding of the biology of these cancers, this research aims to identify new biomarkers and lay the foundation for more personalized treatment strategies for patients with GEP-NENs.

Research project

Potentialisation de la thérapie radionucléidique par la chimiothérapie : effet sur les récepteurs de la somatostatine des tumeurs neuroendocrines

The incidence of neuroendocrine cancers has increased over the last decades in Canada. Mainly localized in the gastrointestinal and pulmonary systems, these tumours develop slowly, which lead to their late detection, frequently at the metastatic stage.

Since conventional treatments were ineffective, more effective approaches such as peptide receptor radionuclide therapy (PRRT) have been developed. It is principally based on the specific targeting of somatostatin receptors present on neuroendocrine tumors (NET), with a radioactive isotope coupled somatostatin-like molecule.

During this internal radiotherapy, the radiation emitted by the radioactive isotope damages DNA and hence kills the cancer cells. Although PRRT is a promising treatment with longer progression-free survival and improved quality of life, the overall remission rate remains low. It is therefore essential to find new ideas to improve the therapeutic effect of PRRT.

To potentiate PRRT, our team explored various chemotherapeutics like temozolomide which increase the number of somatostatin receptors and enhance the uptake of radioactivity by NET cells.

The objective of this preclinical study is to improve the effectiveness of PRRT of NET to allow the most effective strategies to go on clinical trials.