Blood Test Supports Use of New Stomach Cancer Treatment

By measuring the number of copies of just one gene from cancer DNA circulating in the bloodstream, scientists were able to identify the patients with stomach cancer who were most likely to respond to treatment.

Activation of the fibroblast growth factor receptors (FGFRs) is a common oncogenic mechanism, with activation of the FGFRs occurring in a subset of nearly all common cancers. Tumors with multiple copies of the gene FGFR2 responded well to the treatment, with three out of nine patients having a response to treatment, and in those patients the drug worked for an average of 6.6 months.

Scientists at The Institute of Cancer Research (London, UK) and their colleagues assessed the potency of the FGFR tyrosine kinase family inhibitor AZD4547 in patients with stomach and breast cancer in a phase II clinical trial that screened 341 patients. The investigators used a multiplicity of techniques to assess the potency of the inhibitor. They also had access to additional tumor samples from breast and gastric cancer trials.

DNA and RNA was extracted from fresh frozen tumor samples using AllPrep micro DNA/RNA extraction kit (QIAgen, Hilden Germany) and from formalin-fixed paraffin embedded (FFPE) tumor samples using QIAgen’s AllPrep DNA/RNA FFPE extraction kit. Droplet digital polymerase chain reactions (ddPCR) were performed on a QX100 droplet PCR system (Bio-Rad, Hercules, CA, USA). Others techniques employed included Western Blotting, whole exome sequencing, immunoprecipitation, and immunohistochemistry.

Initially using tumor biopsies, the scientists found many copies of the FGFR2 gene in 9% of cancers among the 135 stomach cancer patients on the trial. Cancer cells often undergo changes in their DNA that can result in multiple copies of genes that help cancers grow and spread. Some 18% of breast cancers were found to have multiple copies of a sister gene, known as FGFR1, and not FGFR2, but tumors with multiple FGFR1 genes did not have the same susceptibility to the drug. They found that FGFR2 hijacks molecular pathways that help cancer grow and spread, and some stomach tumors become addicted to high levels of the gene's protein product.

Nicholas C. Turner, PhD, a consultant medical oncologist and co-team leader said, “Our study has identified a potential new treatment for a subset of patients with gastric cancer, and has explained why some gastric cancers were responding to treatment while others did not. We were able to design a blood test to screen for patients who were most likely to benefit from an FGFR2 inhibitor, helping us to target drug therapy at those patients who were most likely to benefit.” The study was published on May 13, 2016, in the journal Cancer Discovery.

Related Links:
The Institute of Cancer Research
QIAgen
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