Drug targets stomach cancer gene 'addiction'

Testing cancers for 'addiction' to a gene that boosts cell growth can identify patients who may respond to an experimental targeted drug, according to research by a team at the ICR and The Royal Marsden

Testing cancers for ‘addiction’ to a gene that boosts cell growth can identify patients who may respond to an experimental targeted drug, according to research by a team at the ICR and The Royal Marsden.

Led by Professor David Cunningham, Director of the NIHR BRC and Consultant Medical Oncologist, and Dr Nicholas Turner, Team Leader in Molecular Oncology at the ICR and Consultant Medical Oncologist at The Royal Marsden, the Phase II clinical trial assessed the potency of the drug AZD4547, an FGFR inhibitor, in 341 patients with stomach and breast cancer.

Stomach cancers with multiple copies of the FGFR2 gene were found to be particularly susceptible to the drug because the tumours had become reliant on, or ‘addicted to’, the gene in order to grow.

6.6 months

the median progression-free survival in stomach cancer patients who responded to FGFR inhibitor drug AZD4547

Initially using invasive tumour biopsies, researchers found multiple copies of the FGFR2 gene in 9% of stomach cancer patients.

These tumours responded well to the treatment: responses were seen in three of the nine patients who received the drug, which prevented tumour progression for an average of 6.6 months.

Some 18% of breast cancers were found to have multiple copies of a sister gene known as FGFR1 but these did not have the same susceptibility to AZD4547.

"This is a great example of a faster, smarter treatment being delivered to a relatively small but important group of patients with gastric cancer"

Further research into why the drug worked well only in certain tumours revealed that FGFR2 hijacks molecular pathways that help cancer to grow and spread, and that some stomach tumours become addicted to high levels of the gene’s protein product. This addiction is a weakness that can be exploited by new therapies.

The researchers also showed that a non-invasive blood test – known as a ‘liquid biopsy’ – could measure the number of copies of the gene from the tumour DNA circulating in the bloodstream in order to identify patients who are most likely to respond to treatment.

Professor Cunningham said: “This is a great example of a faster, smarter treatment being delivered to a relatively small but important group of patients with gastric cancer, made possible through the support of our BRC.”

The study was funded by Cancer Research UK and AstraZeneca, with additional funding from Breast Cancer Now and the NIHR BRC at The Royal Marsden and the ICR.