Professor Gordon Jayson – Ovarian Cancer

Why do anti-VEGF antibodies work in some patients but not in others?

Scientist studying petri dish

Professor Gordon Jayson, Christie Hospital and University of Manchester: Resistance mechanisms to the treatment of ovarian cancer with drugs targeting the tumour vasculature

£199,631 over 24 months

Aims of our research

Angiogenesis is the formation of new blood vessels. The process is essential for tumour growth as it provides food and nutrients and takes away waste products. In some tumours it also allows tumour cells to spread to other organs to form metastases. One of the most important growth factors (like a hormone) that drives blood vessel formation in tumours is called VEGF. This molecule has been targeted by many different drugs of which one of the most well-known is an antibody to VEGF. Clinical trials with this antibody have shown that it delays the recurrence of ovarian cancer but only a proportion of patients benefit from the treatment. We identified a group of patients whose disease was well controlled by the antibody and another group where the drug was ineffective. Our laboratory work suggested that the latter observation was because inhibition of VEGF led to activation of alternative growth factor receptors. This mechanism is the focus of this grant.

Progress so far

Our work has shown in patients’ tumour samples that cancer cells move more quickly when treated with an anti-VEGF antibody if receptor (c-Met) activated by another growth factor, known as HGF, is already active in cells. We have demonstrated this effect in simple laboratory models and are now testing the finding in more complex experiments.

Implications for future prevention, treatment or cure and future work

This work is important because the goal is to understand why anti-VEGF antibodies work in some patients but not in others. Further, the work asks specifically whether c-Met, the receptor for another growth factor, HGF, is responsible for this resistance. Evidence that supported this concept would lead directly to new clinical trials of HGF/c-Met inhibitors either with or instead of VEGF inhibitors; the aim being to generate more effective anti-angiogenic treatments for our patients.