Organoids against cancer in pets and people

It’s not just people who suffer from cancer, our pets do too. What is more, cancers that are considered rare in humans, often occur more frequently in cats and dogs.

That is why, when our veterinary surgeons treat their patients, they don’t just remove the tumor. They subsequently use the diseased tissue, with the owner’s consent, to grow organoids in a lab. These 3D mini-versions of the original tumor show great potential in the field of precision medicine, and can be used to test drugs beneficial to both human and veterinary cancer patients.

Background

Drug development in both human and veterinary medicine continues to rely heavily on laboratory animals to determine levels of safety and efficacy during the pre-clinical phase. Yet even though considerable efforts are being taken to reduce the number of laboratory animals and develop animal-free alternatives to be used in human pharmacological research, very few initiatives exist to limit the use of laboratory animals in the field of veterinary medicine. 

Organoids, human- or animal-based, have been shown to have great potential as viable models to test new and existing substances, while also providing much needed sample heterogeneity as seen between patients. Organoids are miniature 3D structures grown from (cancer) stem cells, that consist of organ-specific cell types with spatial organizations and cell-cell interactions similar to the in vivo organ or tumor. Organoids are therefore able to recapitulate specific organ/tumor functions and growth mechanisms. Organoids are a highly suitable model to perform in vitro high-throughput drug screenings, reduce the need for animal experimentation, and allow for strict control and manipulation of study conditions.

By using diseased tissue recovered as part of regular veterinary treatment, organoid generation might become a valid alternative to using laboratory animals during pre-clinical drug evaluation.

The challenge: various types of canine adrenal tumors

With the incidence of approximately 2% of all canine tumors, adrenal tumors represent a common diagnosis in a veterinary practice and the impact on the quality of life of dogs is severe. Most of the adrenal tumor types are hormonally active and involve cortisol and catecholamine excess. Cortisol-secreting adrenocortical tumors resemble hypercortisolism or so-called Cushing’s syndrome. Uncontrolled secretion of cortisol causes excessive drinking and urinating, polyphagia, muscle wasting and alopecia. Catecholamine-secreting adrenal tumors originate from the adrenal medulla and are called pheochromocytoma. Clinical signs include hypertension, abdominal pain, and cardiac abnormalities. Adrenal tumors can also be hormonally silent and are usually detected by chance during diagnostic imaging.

Adrenal tumors are potentially malignant, and thus life threatening. As such, the best treatment option for all types of adrenal tumors remains surgery. This, however, is not without risk and can only be performed at highly specialized institutions, and thus not widely available. Furthermore, in case of co-morbidities, metastasis, invasion of the adrenal tumor in adjacent blood vessels and/or organs, surgery is not possible. In these situations, we are confronted with the fact that, at present, there exists no medicinal treatment to suppress adrenal tumor growth in dogs. There is an urgent need to develop new medicinal treatment modalities for canine adrenal tumors.

Adrenal organoids as a reliable lab animal free alternative

To assess the potential of adrenal tumor-targeting drugs, we need a reliable, stable, and relevant in vitro system. In the last decade, considerable advancements in cell culture techniques have been made, leading to the development of so-called organoids.

In the current initial study, we aim to demonstrate the value of using patient-derived tissue to grow organoids as an innovative and reliable animal-free alternative for pharmacological drug testing, using canine adrenal tumor organoids as a proof-of-concept.

The impact of a One Medicine approach

We believe our innovative approach to culture, validate, and apply adrenal organoids as a model for adrenal cancer, has the potential to greatly improve canine health, without having to resort to the use of laboratory animals.

What is more, this research is likely to advance human oncological research, too. As it stands, the mortality rate in humans with adrenal cancer is equally high, with survival a mere five years following diagnosis. Not surprisingly, finding a medicinal treatment for adrenal cancer is also one of the top priorities in human oncology. However, as adrenal cancer is a rare disease and tissue availability is low, current research efforts remain slow and inefficient.

As dogs and humans have identical adrenal gland anatomy and physiology, with considerable similarities in adrenal cancer between the two species, advances in treatment options for dogs will likely have considerable translational benefits to human oncology research and medicine, too.

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