19/05/2022: Glasgow PhD Opportunity

Use of anti-VEGF Tyrosine Kinase Inhibitors in dogs.

A wide range of therapies are now used to treat cancer successfully in human patients. However, these same therapies are associated with a significantly increased risk of developing new-onset heart failure. Cardio-oncology is a relatively new clinical discipline which aims to understand the mechanisms that underlie the cardio-toxic side effects of cancer therapies alongside optimising the cardiovascular risk management in cancer patients.

Anti-VEGF tyrosine kinase-inhibiting (TKI) drugs have revolutionised treatment of various solid malignancies in human medicine. Anti-VEGF TKIs inhibit the vascular endothelial growth factor (VEGF) signalling pathway and have anti-angiogenic effects. Cardio-toxicity represents a clinical challenge in the growing number of cancer survivors when using anti-VEGF TKIs, Although the survival benefits conferred by anti-VEGF TKIs are clear, clinical consideration should be applied to assess treatment-associated cardiovascular risks particularly in elderly patients where co-morbidities are more common. Indeed, anti-VEGF TKIs are now recognised as causing adverse events including congestive heart failure. TKIs are being increasingly used in veterinary oncology with the licensing of two new drugs (toceranib, masitinib) for dogs, one of which (toceranib) has anti-angiogenic activity against VEGFR and has a similar activity profile to the human-licensed drug sunitinib. Although a preliminary report suggests toceranib can cause hypertension the full implications for cardiac-related function and outcomes are unknown. 

This PhD studentship will bring together veterinary oncologists, human cardiologists and basic scientists to understand the effect of anti-VEGF TKIs on cardiac function. In particular, the successful applicant will determine cardiac function in dogs undergoing treatment with TKIs, utilise human clinical trial samples and data from patients undergoing treatment for anti-VEGF TKIs, and perform in vivo and ex vivo cardiac research using laboratory animal models of cardiac disease.
 

Supervisors: 
Prof. Jo Morris DipECVIM-CA (oncology): Joanna.Morris@glasgow.ac.uk 
Prof. Christopher Loughrey: christopher.loughrey@glasgow.ac.uk
 

Please contact us for more information.
Start date:  October 2022 - but negotiable