Today, some breast cancer patients with BRCA mutations and triple negative cancers are treated with Poly (ADP-ribose) Polymerase (PARP) inhibitors, which trap and destroy PARP-1, an important enzyme for DNA repair that cancer cells rely on for survival. Similarly, therapeutics that target glutaminase, an enzyme feeding some triple negative breast cancers, are also being developed. However, no method currently exists to measure these enzyme expression levels in patients. Having a biomarker to quantify those levels would help identify those most likely to benefit from targeted therapies in a non-invasive way.
In the first study (Abstract #851093), researchers from the Penn's department of Radiology and the Abramson Cancer Center used PET imaging and a novel radioactive tracer known as [18F]FluorThanatrace (FTT), to measure PARP-1 levels in 30 women with breast cancer with various subtypes before therapy, including surgery.
FTT - Author - Robert - H - Mach
FTT -- which was developed by co-senior author Robert H. Mach, PhD, the Britton Chance Professor of Radiology at Penn -- binds to PARP-1, making it visible on a PET scan. The researchers correlated the FTT uptake in the breast cancer patients with untreated surgical specimens that had been immunostained for PARP-1 in the lab. They found that the PET imaging agent could effectively visualize and measure PARP-1 levels in all breast cancer tumors and metastases.
Past studies from the same team of researchers have linked PARP-1 levels to targeted therapy resistance and shown FTT's ability to quantify PARP expression levels in ovarian cancer.
Study - Validation - FTT - Method - PARP-1
"This study provides early validation of FTT as a quantitative method to measure PARP-1 expression in breast cancer," said first author Elizabeth McDonald, MD, PhD, an assistant professor of Radiology at Penn. "Importantly, it also shows that the level of PARP-1 expression varies considerably within a given breast cancer subtype and that, surprisingly, any subtype can have high PARP-1 expression."
Many clinical trials with...
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