New sheep model aids development of targeted cancer therapy

A sheep model of lung cancer could provide a new platform for developing and testing treatments delivered directly into tumours, researchers have shown.

Scientists from the Roslin Institute, Royal (Dick) School of Veterinary Studies and Moredun Research Institute used a lung tumour of sheep, ovine pulmonary adenocarcinoma (OPA), to develop image-guided techniques for delivering anti-cancer drugs such as cisplatin directly into lung tumours.

The study showed that chemotherapy could be delivered successfully, aided by CT imaging, through the chest wall – transthoracic – or via the airways – transbronchial – while allowing researchers to monitor drug distribution throughout the tumour, and elsewhere in the body.

Direct delivery resulted in therapy reaching targeted tumours while reducing exposure in the bloodstream, compared with conventional intravenous administration.

The findings provide proof-of-concept that the OPA model could help bridge the gap between conventional preclinical studies and clinical evaluation of new approaches to treating lung cancer.

Cisplatin, which has been used to treat cancer for decades, is normally administered intravenously, meaning that the drug circulates throughout the body. Although this enables the drug to reach tumour cells, healthy tissues are also exposed, contributing to potentially dose-limiting side effects.

Delivering chemotherapy directly into a tumour, known as intratumoural drug delivery, offers a potential alternative treatment strategy, which could reduce exposure in other systems of the body while allowing effective drug concentrations within the tumour.

Techniques for injecting cisplatin directly into lung tumours are beginning to be evaluated in patients, but further preclinical research is required to optimise these approaches before they can be adopted more widely.

Small animal models remain essential to cancer research, but their size limits the use of many of the techniques used to diagnose and treat lung cancer in people.

Sheep offer an important complementary research model. Their lungs are similar in size to those of humans, and share important anatomical and physiological characteristics, enabling researchers to use clinically relevant CT imaging, bronchoscopy, and image-guided interventions.

OPA shares pathological and molecular characteristics with some forms of human lung adenocarcinoma, making it a valuable comparative disease. 

The researchers subsequently tested whether the model could support long-term studies in which an animal could be monitored following treatment.

One sheep received two intratumoural cisplatin treatments two weeks apart, with tumour biopsies, repeated blood sampling and CT imaging performed over a 28-day period.

Tumour volumes decreased during the study, with the experiment also demonstrating that repeated intratumoural treatment, biopsy acquisition and longitudinal CT monitoring could all be undertaken within the same animal.