Researchers at the Stony Brook Cancer Center have designed a novel multi-targeted therapy for non-small cell lung cancer (NSCLC) that reduced tumors by more than 95 percent in a laboratory model and appears to halt drug resistance, according to findings published in August 2026 in the journal Molecular Therapy.
Development and Mechanism of Gem-miR-129
Led by Jingfang Ju, PhD, professor in the Department of Pathology in the Renaissance School of Medicine at Stony Brook University, the research team engineered a therapeutic agent by combining a natural tumor suppressor molecule, miRNA-129, with a standard chemotherapy drug, gemcitabine. According to the study, the resulting molecule—named Gem-miR-129—enters cancer cells independently without requiring a delivery vehicle.
Once inside the cell, the agent simultaneously shuts down three distinct oncogenic driver proteins responsible for tumor growth and therapy resistance: HMGB1, YAP1, and PBX3. Dr. Ju noted that the molecule achieved a tumor shrinkage rate exceeding 95 percent in a murine model of non-small cell lung cancer, while increasing survival time by many weeks.
Combating Drug Resistance in Lung Cancer
Drug resistance is the primary reason why current lung cancer therapies stop working for cancer patients. While current standard treatments often include gemcitabine chemotherapy or tyrosine kinase inhibitors (TKIs) for patients carrying epidermal growth factor receptor (EGFR) mutations, approximately half of these cancers eventually acquire resistance to TKIs.
Gem-miR-129 is specifically designed to target tumors that have developed resistance to TKIs and standard chemotherapy. According to Dr. Ju, once the gemcitabine component is released from the hybrid molecule, low-dose gemcitabine inhibits tumor-infiltrated T regulatory cells (Ti-Tregs). These regulatory cells normally block cytotoxic CD4 and CD8 T cells from destroying cancer cells. By suppressing Ti-Tregs, the therapeutic agent restores the immune system’s ability to reduce tumor burden without producing noticeable toxic side effects in the laboratory model.
Pathway to Clinical Trials
Following the successful results in animal models, the research team’s next objective is to pursue Investigational New Drug (IND) studies. The IND process is designed to establish a drug’s safety profile with the hopes of gaining regulatory approval for human clinical trials. The research received financial support from a Veterans Affairs Merit Award and a Stony Brook Cancer Center Pilot Fund.
