Wistar Scientists Identify New Mechanism Behind Chemotherapy Resistance in Ovarian Cancer

Excerpt from the Press Release:

PHILADELPHIA — (JULY 23, 2026) — Scientists at The Wistar Institute have identified a new mechanism behind the chemotherapy resistance that makes ovarian cancer so lethal. In a new study, funded by top cancer research foundations and published in The Journal for ImmunoTherapy of Cancer, the researchers showed that chemotherapy triggers an inflammatory cascade that recruits immune cells into the tumor microenvironment, which ultimately function to protect the cancer from subsequent chemotherapy. Notably, this finding could improve outcomes for patients because the molecular pathway the researchers discovered has the potential to be blocked using drugs already in clinical use for other diseases.

“Traditionally, chemotherapy resistance has been seen as a cancer-cell problem,” said Nan Zhang, Ph.D., assistant professor in the Ellen and Ronald Caplan Cancer Center’s Molecular and Cellular Oncogenesis Program and senior author on the study. “Our findings suggest it is also an immunology problem. The treatment meant to kill the tumor can trigger inflammatory responses that help it survive. The encouraging news is that there are already approved drugs that may be able to target this pathway and restore chemotherapy sensitivity.”

High-grade serous carcinoma is the most common and deadly subtype of ovarian cancer. Many patients respond initially to first-line treatment, chemotherapy, but the majority go on to develop recurrent disease that resists subsequent chemotherapy. Although tumor-intrinsic genomic, epigenomic, and transcriptional alterations contribute to chemoresistance, prior research has found limited genomic divergence between primary and recurrent tumors, suggesting that chemoresistance is also acquired by microenvironmental mechanisms. As a result, researchers such as Zhang, have increasingly secured funding to look beyond the cancer cells themselves, to the surrounding tumor microenvironment, for answers.

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