Preclinical study identifies new target for recurrent ovariancancer pennmedicine
PARP inhibitors , a newer type of targeted standard of care treatment, have increased survival for, but, similar to chemotherapy, these therapies eventually stop working for many patients, leaving them without treatment options.
To combat these challenges, this study focused on the protein B7-H4, which—as pivotal work from co-author and collaborator Daniel J. Powell Jr., Ph.D., an associate professor of Pathology and Laboratory Medicine, has shown—is a potentially high impact target that is found in the majority of breast and ovarian cancers at diagnosis.
The team used matched samples from the Penn Ovarian Cancer Research Center Tumor BioTrust Collection, to see if B7-H4 was found in tumor tissue from the same patients before, during, and after treatment—and in some cases in the setting of end-stage metastatic disease. They found that B7-H4 was overexpressed in 92 percent of high grade serous ovarian carcinoma tumors analyzed at diagnosis and maintained high levels throughout the course of cancer treatment, even following chemotherapy or PARPi.
In 61 percent of PDX models that hadn't received any previous PARPi or chemotherapy treatment, the tumors decreased in size after just one dose. With continued treatment every 28 days, to better mimic clinical dosing, the drug resulted in significant tumor regression and increased survival in
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