New imaging tools that track key breast cancer enzymes may help guide treatment

emerging set of diagnostic tools could help identify breast cancer patients who are most likely to benefit from treatments that promote a range of subtypes of important enzymes, including BCRA mutations and triple negative cancers. The new study, conducted by researchers at the University of Pennsylvania's Perelman School of Medicine, was presented yesterday at the San Antonio Breast Cancer Symposium.some patients with BRCA mutations and triple-negative breast cancers are treated with poly (ADP-ucose) polymerase (PARP) inhibitors, which capture and destroy PARP-1, an important enzyme for DNA repair on which cancer cells depend. Similar treatments are being developed for glutaminease, an enzyme that feeds some triple-negative breast cancers. However, there is currently no way to measure the performance levels of these enzymes in patients. Having a biomarker to quantify these levels will help identify those most likely to benefit from non-invasive targeted therapy.In the first study ( abstract 851093), researchers from the Department of Radiology at the University of Pennsylvania and the Abramson Cancer Center used PET imaging and a new radioactive tracer called Fluor Thanatrace (FTT) to measure pre-treatment PARP-1 levels in 30 patients with different subsypes of breast cancer, including surgery.The FTT, developed in collaboration with Dr. Robert H. Maher, a professor of opportmiss radiology at Pennsylvania State University, combines with PARP-1 and is visible in PET scans. The researchers linked FFT intake in breast cancer patients to surgical specimens of untreated PARP-1 immuno-staining in the lab. They found that PET spectratives were effective in showing and measuring PARP-1 levels in all breast cancer tumors and metastasis.past studies from the same research team have linked PARP-1 levels to drug resistance in targeted treatments and shown that FLT can quantify parp performance levels in ovarian cancer., assistant professor of radiology at Pennsylvania State University, said: "This study provides early validation of FFT as a quantitative method of performing PARP-1 in breast cancer. Importantly, it also shows that PARP-1 levels of expression vary widely within a given breast cancer subsype, and surprisingly, any subsype can have a high PARP-1 performance.Many clinical trials of PARP-1 focus only on tri-negative subtypes. However, this new study suggests that some ER-positive cancer patients, for example, who may have high levels of PARP-1 may therefore benefit from this targeted treatment.addition, these results provide unrideated evidence that performance levels vary widely between carriers of BRCA mutations, which is important because BRCA status is often used as a criterion for selecting PARP inhibitor therapy, McDonald said.Abstraction in the second study, another group of researchers from the University of Pennsylvania used a radioactive tracer, fluciclovine, as a measure of tumor imaging agent glutamine level PET imaging in breast cancer mouse models based on knowledge of some tristasical breast cancers relying on glutamine for survival and growth.although CFDP has been approved by the FDA for prostate cancer imaging, its ability in other cancers is not yet clear. The reagent is transferred through glutamine and undergoes minimal metabolism to enter and expel the protein from the cells.university in Pennsylvania used the visible agent to observe the effects of glutamine inhibitors (CB-839) on glutamine levels in triple-negative breast cancer. Glutaminease is considered a "drugable" target because it is a key enzyme for glutamine decomposition, which is the way cancer cells metabolize glutamine and small molecule drugs.The assessment of the size of the tumor glutamine pool will inform the pharmacological effects of glutamine inhibitors, as treatment can lead to elevated levels of glutamine in tumors," said Dr. Rong Zhou, an associate professor of radiology at Pennsylvania State University. This imaging method may provide an accurate medical tool to tell doctors early which patients are responding and which are not.researchers found that CFCs were effective in tracking the response of tumor glutamine levels to glutamine inhibition. For example, after CB-839 was given, the cell's intake of CFCs increased, consistent with higher concentrations of glutamine and lower levels of enzyme activity in triple-negative breast cancer cells. Metabolic drugs such as glutamine inhibitors take longer to affect tumor size than chemotherapy, which typically shrinks tumors quickly and is evaluated by measuring tumor size. Therefore, a non-traumatic approach to detecting the early response of these drugs would be useful, Zhou said."These studies are an important step in developing much-needed non-invasive imaging tests to help measure and predict inhibitory responses and guide the treatment of women with a wide range of breast cancers," said Dr. David Mankoff, a professor of radiology at Pennsylvania State University. Senior author of two abstracts. Ongoing research at Pennsylvania State University will continue to expand these results and help us get closer to potential clinical applications. Some of McDonald's research was supported by Susan G. Koeman's Cure Award (CCR 16376362), the Renchen Ray Society Scholars Award, the NCI Cancer Center (P30 CA016520), and the Department of Radiology at the University of Pennsylvania. Zhou's research is supported by NCI (R21CA196563, R01CA211337). Both studies were supported by the Komen Leadership Award (SAC1300 60). (This net special article)