Each of our research themes contribute to our specialist translational research programmes which leave a lasting legacy for patient benefit.
Liquid biopsy profiling for detection and stratification of cancer
Our expertise in profiling of mutations and gene amplification in circulating free DNA has been a critical facilitator in developing the concept of the liquid biopsy. This has been used for early detection of relapse in breast cancer patients up to 2 years ahead of clinical relapse, giving a wider therapeutic window for intervention (Coombes et al, 2019). The national £13M TRACERx phylogenetic lung cancer study (Abbosh et al, 2017) provided the first evidence that ctDNA profiling could identify sub-clonal dynamics and chemotherapy resistance prior to CT scanning, with intratumoural heterogeneity in lung cancer linked with increased risk of death (Hanjani et al, 2017).
We are a leading international centre focussed on the development of agents that can delay or prevent cancer. Through our novel strategies to define optimal dosing and surrogate biomarkers of potential efficacy, we have delivered innovative clinical trials in high-risk populations. A major highlight has been the demonstration of a nonlinear dose response for the protective effects of the dietary agent resveratrol in mouse models and human window trials, establishing the new paradigm that “more is not better” in therapeutic prevention (Cai et al 2015).
Precision therapeutics for mesothelioma
The Mesothelioma Stratified Therapy (MiST) trial is the first of its kind, offering a multi-arm stratified therapy trial for patients with relapsed malignant mesothelioma (clinicaltrials.gov). The goal of MiST is to enable acceleration of novel, effective personalised therapy as a basis for improving survival outcomes for patients with mesothelioma.
B cell malignanicies
Our haemato-oncology specialists have made key contributions in improving outcomes for B cell malignancies. We have led on early phase studies of BTK (Bruton’s tyrosine kinase) inhibition in mature B-cell malignancies, which have now transformed the treatment of CLL (chronic lymphocytic leukaemia) with many patients entering durable remission (Walter 2016, Walter 2017).
Pre-clinical models enabling drug and biomarker discovery
Pre-clinical models that accurately predict patient outcomes including immunotherapies are much sought after and hence a major strategic investment (~£2M) has been made in patient-derived explants that contextually preserve tumour architecture (Karekla et al, 2017, Powley et al, 2020).
A further snapshot of impactful research working towards patient benefit can be found below:
- Tremelimumab for relapsed malignant mesothelioma (DETERMINE trial)
- Panitumumab in metastatic colorectal cancer (ASPECCT trial)
- Vorinostat in malignant mesothelioma (VANTAGE-014 trial)
- Liquid biopsy standardisation
- KRAS 12D expression in lung resident myeloid cells
- Dysregulation of immunity genes in chronic lymphocytic leukaemia