Emerging evidence suggests that the early adaptation of cancer cells to overcome prolonged and severe oxidative stress, via increased antioxidant capacity and angiogenesis, plays an important role in the mechanisms of resistance to many standard chemotherapeutic agents. We therefore believe that non-invasive imaging of these processes could help us to detect the emergence of drug resistance and aid trials of exciting new therapies that counteract these adaptive responses, leading to better outcomes for cancer patients.
Targeting the tumor vasculature is an attractive treatment option, with anti-angiogenic agents providing a means not only to prune immature vessels but also to induce a window of “vascular normalization”. However, although anti-angiogenic therapies have been extensively trialled, they have not yet lived up to their promise. Two key obstacles in this regard are tumour heterogeneity and the lack of validated imaging biomarkers that can characterise this heterogeneity. Addressing these obstacles would help to:
- Predict drug response;
- Characterise heterogeneity of response;
- Optimise drug dosing;
- Monitor response to therapy.
By directly imaging the tumour blood supply, our approaches will enable new insights into the mechanism of action and scheduling of drugs that target the tumour vasculature, particularly in the neo-adjuvant setting.
Ben Woodhams, Emma Brown, Lina Hacker, Dr Joanna Brunker, Dr Rajesh Shahapure.
Dr Alasdair Russell, Prof. Carlos Caldas, Prof. Kevin Brindle (CRUK CI); Dr Oshaani Obeyakoon, Prof. Fiona Gilbert (Department of Radiology, University of Cambridge); Dr James O’Connor, Prof. Geoff Parker (University of Manchester).