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Researchers at the Perelman School of Medicine have identified a new drug target for treatment-resistant Ovarian cancer. Credit: Mehak Dhaliwal

A preclinical study conducted by researchers and scientists at the Perelman School of Medicine identified a new drug target for treatment-resistant ovarian cancer.

Cancer drugs called PARP inhibitors have previously been extremely successful in improving the likelihood of survival for patients with ovarian cancer. Over time, however, cancer cells become resistant to the PARP inhibitors, thereby significantly decreasing their efficacy.

The researchers examined samples from the Penn Ovarian Cancer Research Center Tumor BioTrust Collection, finding that that a protein B7-H4 was “overexpressed in 92 percent of high grade serous ovarian carcinoma (HGSOC) tumors analyzed at diagnosis and maintained high levels throughout the course of cancer treatment, even following chemotherapy or PARPi.” 

The overexpression of B7-H4, coupled with the protein being located on the outside of cancer cells, makes it an extremely viable target for a drug to bind to.

Once this new drug target was identified, researchers used a new class of immunotherapy drugs called antibody-drug conjugates to target B7-H4 in 20 cancer models derived from real patients. The results from the study were promising, with 61% of the models showing a decrease in tumor size after one dose. After 28 days of consistent treatment, the antibody-drug conjugate led to “significant tumor regression and increased survival.”

"We saw excellent anti-tumor activity, sustained over a long period of time in models that are drug-resistant, which is uncommon," Sarah Gitto, a pathology and laboratory medicine instructor at Penn, told Labiotech. “We’ve been able to show that B7-H4 is a very robust and widespread target that can be used across multiple stages of patient care.”

Ovarian cancer ranks fifth in cancer deaths among women. Often, patients have already had ovarian cancer and experience a return — something that these researchers hope to help address. A previous study by Penn researchers found that an odor test can detect compounds found in pancreatic and ovarian cancer cells using blood samples from patients.