Detecting tumour resistance to treatment with positron emission tomography. (360G-Wellcome-107610_Z_15_Z)

£1,137,496

Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States and Europe, making it one of the most common cancers affecting women. Ovarian cancer initially responds well to surgical resection and/or platinum-based chemotherapy, leaving the patient disease free. However, tumours often recur as lethal, platinum-resistant disease. Aldehyde dehydrogenase (ALDH) has been identified as a biomarker of chemoresistance in this patient population. I will develop nove l positron emission tomography (PET) imaging agents with high specificity and selectivity for visualising therapy resistance in preclinical models of ovarian carcinoma, based on the measurement of aldehyde dehydrogenase activity. Additional biomarkers of drug resistance, such as the drug efflux transporter MDP1, are also known to have a major impact on the pharmacological behavior of most of the drugs in use today. We will further compare the lead ALDH imaging agent to a previously validated PET radiotracer, designed at UCL for the noninvasive assessment of MDP1 activity, to determine their clinical utility. Following clinical translation, an imaging biomarker of treatment resistance will help stratify patients into those suitable for second-line therapy, with high likelihood of response, allowing long term personalised patient management and the possibility of reducing mortality and morbidity.

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Grant Details

Amount Awarded 1137496
Applicant Surname Witney
Approval Committee Sir Henry Dale Fellowship Interview Committee
Award Date 2015-05-27T00:00:00+00:00
Financial Year 2014/15
Grant Programme: Title Sir Henry Dale Fellowship
Internal ID 107610/Z/15/Z
Lead Applicant Dr Timothy Witney
Partnership Name Royal Society/Wellcome Trust Sir Henry Dale Fellowship
Partnership Value 1137496
Planned Dates: End Date 2018-10-21T00:00:00+00:00
Planned Dates: Start Date 2015-07-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Raymond MacAllister