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Jumonji C Inhibitors and Chemotherapy-Resistant Lung Cancer

For many patients with lung cancer, resistance to chemotherapy is a primary cause of treatment failure. Researchers at UT Southwestern Medical Center in Dallas are using a 35-gene signature to identify tumor cells most likely to develop resistance to treatment. Their findings, which were published in Cell Reports, suggest a new potential therapeutic target—Jumonji C enzymes. As chemoresistant cells appear to be dependent on these enzymes for survival, inhibiting them may prove to be an effective therapy.

The investigators studied mouse and cellular models of non–small cell lung cancer and developed a series of cellular models of progressive tumor resistance to standard chemotherapy. Then they found genes commonly altered during the development of resistance and identified a 35-gene signature, which indicated a higher genetic likelihood of chemotherapy resistance.

As cancer cells developed greater resistance to chemotherapy, they progressively made higher amounts of Jumonji C lysine demethylases. Two potential treatments, both Jumonji C inhibitors, were tested by these researchers.

"We think these Jumonji C inhibitors have the potential to be used either to treat tumors once they become resistant to standard therapies or to prevent resistance altogether," said study senior author Elisabeth D. Martinez, PhD, Assistant Professor of Pharmacology and the Hamon Center for Therapeutic Oncology Research at UT Southwestern.