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Small Animal Internal Medicine

Insulinoma: Molecular Aspects and Recent Data on Diagnosis and Treatment

Thursday, June 15, 2023

1:45 PM – 2:45 PM ET

Location: PCC 111AB

CE: 1

Primary Presenter(s)

Insulinoma is the most common pancreatic neuroendocrine tumour in dogs and humans. The use of canine insulinoma has been validated as translational model for human malignant insulinoma.

Current treatment options are limited to surgery and palliative medical therapy and survival is poor (median of 4 [range 0-18] months and 14 [range 0-51] months for medically and surgically treated dogs, respectively).

Studies from the past decade have improved our understanding about driving factors and critical survival genes in insulinoma, which ultimately will be translated to new, more precise insulinoma treatments. Most important findings from these studies are:

CD90 is a putative cancer stem cell marker and therapeutic target in insulinomas. Anti-CD90 monoclonals form a potential novel adjuvant therapeutic modality by targeting either insulinoma cells directly, or by targeting the insulinoma microenvironment.

Another subpopulation of cancer stem cells from canine and human insulinomas exhibited overexpression of Notch-signaling related genes and inhibition of the Notch pathway enhanced the sensitivity of these cancer stem cells to 5-fluorouracil (5-FU). These findings suggested that the combined strategy of Notch signaling inhibition and 5-FU synergistically attenuated enriched INS cancer stem cell populations, providing a rationale for future therapeutic exploitation.

RNA sequencing of canine insulinomas demonstrated similar genetic profiles in normal pancreas and early clinical stage primary insulinomas, whereas late clinical stage primary insulinomas resembled the genetic profile of metastatic lymph nodes. These findings suggest that markers of malignant behavior can be identified at the primary site of the disease.

Although it will take years before these fundamental findings will be translated into clinics, recent clinical studies have already made a direct impact on the diagnostic work-up and treatment of canine insulinoma. It has been demonstrated that triple-phase contrast-enhanced CT (CECT) scans have superior outcome in predicting the correct location of the insulinoma within the pancreas, over single- or double-phase CECT-scans in pre-operative imaging of canine insulinoma. It is of utmost importance to determine the exact location of insulinomas when considering laparoscopic excision of a canine insulinoma, as it affects the decision to perform an open or laparoscopic surgical approach. Laparoscopic resection of canine insulinoma is gaining popularity since several large case series in the human field have demonstrated clear advantages of laparoscopic pancreatic surgery over the open approach.

understand the recent advances that have been made to improve our knowledge of driving factors and critical survival genes in canine insulinoma.
understand the importance of triple-phase contrast-enhanced CT in the diagnostic work-up of canine insulinoma.
understand new developments in the identification of novel methods and strategies to improve the prognostication and personalised treatment of canine insulinoma.