Sea Turtle Hospital: the cancer unit

This project aims to harnesses proven human cancer research approaches to identify drugs to treat sea turtles with FP tumours. This project will underpin a larger study to support the conservation of sea turtles by treating individuals with FP, and elucidating the relationship between the herpesvirus, habitat-degradation and tumour development.

Four sea turtle species are endangered or critically endangered, two are vulnerable, and one is data deficient (IUCN Red List). Fibropapilloma has been recorded in all seven species. The spread of FP represents a critical oncological threat, which undermines conservation efforts and requires an urgent response. Surgically treating and rehabilitating all turtles with FP is not feasible, and generally only stranded turtles enter rehabilitation hospitals. As FP triggers are environmental it is likely that, once released, rehabilitated turtles will again develop tumours. Therefore, it is vital that rapid, inexpensive treatments for FP are developed that can contribute effectively to turtle conservation. Pharmacological intervention has the potential to be more widely applicable than surgery, even in widely dispersed populations, and the mainly external nature of FP means drugs can be easily delivered directly into the tumours. Generating high-throughput genetic tumour and viral sequence data will help resolve the etiology of FP.

Green sea turtles (Chelonia mydas) are the species most affected by FP, but it also occurs in all other sea turtle species and its geographic range is spreading. Currently, surgery is the primary treatment for turtles with FP, but almost 40% of turtles that have tumours surgically removed experienced regrowth. The regrowth occurs within an average of 36 days, but since records were only for the relatively short period of captivity it is likely that the true occurrence of regrowth is much higher. Therefore, novel therapies are urgently needed to enhance the outcome of turtles with FP. Human oncology has proven that adjunct pharmaceutical therapy can improve patient outcomes post-surgery. Indeed, in a number of cases anti-cancer drugs alone (without surgery) are sufficient to cure patients. This is especially true for more benign non-metastatic cancers. FP in turtles in many respects resembles non-metastatic cancer; although numerous lesions occur in each individual these are thought to be de novo primary tumours, no metastatically-spread secondary tumours. In addition, tumours primarily occur on the bodies extremities, and in the rare cases where tumours are found on internal organs (~25% of turtles with FP) they are again thought to be primary tumours and not the result of metastatic disease. The benign nature of FP, with the physical effects of the tumours leading to mortality, rather than aggressive tumours themselves, suggests that it would respond well to drug therapeutic treatments. Therefore, the aim of this study is to determine the most effective drug treatment for turtles with FP. To achieve this we will employ the most recent and effective approaches in human cancer therapeutic research: genomic- and network-based precision medicine. We have previously successfully implemented these approaches in the human setting.

• The establishment of an FP tumour bio-bank, by collecting tissue samples from turtles undergoing surgical tumour-removal. Samples from various tumour stages, classes and patient-matched non-cancerous tissues will be stored to meet the subsequent objectives of this project and provide a valuable resource for future research.
• Selected green turtle tumour samples, representative of the development of the disease, will be used to conduct transcript-wide RNA-sequencing. The data will be mapped onto both the green turtle and FP herpes virus genome, providing information on the contribution of both host and pathogen oncogenic signalling components.
• Our proven network-based therapeutic target discovery approaches will be used to identify the driving molecular regulators of FP tumours. We will thereby determine signalling vulnerabilities which can be therapeutically targeted. Vulnerabilities targeted by the most cost-effective drugs will be prioritised for trials in FP tumours.
• We will conduct trials of the lead drug in FP turtles, comparing the effectiveness of 1) the drug only, 2) the surgery only, and 3) post-surgery drug treatments. The trial will be during the period of the grant, but longer-term follow-on data will also be generated.
• Increase general public awareness of marine conservation issues, with a special focus on sea turtles and the FP threat. Disseminate the findings of the project to the general public, scientific community and sea turtle conservation activists and clinicians.