The work was performed in partnership with The Royal Marsden NHS Foundation Trust and the Mount Vernon Cancer Centre, and funded by the National Institute for Health Research.

Anti-angiogenic drugs work by cutting off a tumour’s blood supply, but patients vary in their response to these treatments. While some tumours shrink, others treated with the same drug may continue to grow, and some that respond initially eventually start to grow again. There is little understanding of why tumours respond so differently.

In the new study, published in the British Journal of Cancer, scientists examined 56 individual tumours sampled from 23 patients with metastatic renal cancer. They looked at the effect of anti-angiogenic agents on the tumour’s blood supply and how much the tumour shrank or grew. Based on this work, the authors propose reasons why tumours respond differently to this treatment. Senior author Dr Andrew Reynolds, who leads the Tumour Biology team in the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR), said:

“If the tumour’s blood supply is reduced by the treatment, the tumour can shrink. However, sometimes the tumour does not shrink significantly even when the drug induces a significant reduction in blood supply, so tumours can adapt to survive even when their blood supply is significantly reduced. We also see that sometimes the drug has little or no effect on the blood supply, showing that tumours can also survive the treatment because their blood vessels are resistant. Understanding the nature of these subtle differences is important for developing better treatments.”

The study also sheds light on why tumours that respond initially to treatment can eventually start to grow again. Dr Reynolds said:

“We found that although blood vessels can be killed by this treatment, leading to tumour shrinkage, eventually these blood vessels can grow back, leading to tumour re-growth. Moreover, in tumours that shrank more initially, vessel re-growth was more aggressive. Again, this may have consequences for designing better therapies.”

Strategies to optimise the use of current treatments are being devised by the study’s first author, Dr Naveen Vasudev, who is now Clinical Associate Professor and Honorary Consultant in Medical Oncology at the Leeds Institute of Cancer & Pathology. He said:

“There is currently no way of predicting whether a patients’ tumour is going to respond to an anti-angiogenic drug. A test (based on a gene or protein, for example) that can determine this would be very helpful, since non-responding patients can be spared unnecessary side-effects and, potentially, be offered other types of treatment. Understanding more about the underlying biology governing response and resistance is essential to help achieve this.”