New approach shows promise in fighting lung cancer

A new study from Stony Brook Cancer Center presents a promising approach to combat lung cancer, particularly non-small cell lung cancer (NSCLC). The research team, led by Jingfang Ju, a professor in pathology at Stony Brook University, has developed a novel therapy that targets drug resistance in NSCLC by using a multi-targeted and multimodal miRNA-129 based treatment.

The therapy, named Gem-miR-129, combines a naturally occurring cancer-fighting molecule (miR-129) with a commonly used chemotherapy drug, gemcitabine. This unique approach allows the drug to enter cancer cells without the need for a delivery vehicle, while simultaneously inhibiting three oncogenic driver proteins that contribute to cancer growth and therapy resistance—HMGB1, YAP1, and PBX3.

In laboratory tests on a NSCLC mouse model, Gem-miR-129 demonstrated remarkable results, with tumor shrinkage exceeding 95% and increased survival time for the mice by several weeks. In humans, gemcitabine is the standard first-line chemotherapy for NSCLC patients, and recent advancements in targeted therapies have improved survival for some patients with significant oncogenic driver mutations. However, about half of these cancers develop resistance to targeted therapies, such as tyrosine kinase inhibitors (TKIs).

Gem-miR-129 is specifically designed for NSCLC tumors that acquire TKI resistance, preventing resistance by suppressing oncogenes associated with both intrinsic and acquired resistance to both chemotherapy and EGFR inhibitors. By releasing the low-dose gemcitabine from Gem-miR-129, the therapy inhibits tumor-infiltrated T regulatory cells, which block cytotoxic T cells from eliminating tumor cells. This reduction in inhibitory effect allows the immune response to better target and reduce tumor burden.

The therapy's potential for eliminating resistance and lack of noticeable toxic side effects make it a highly promising approach for future studies and clinical trials. The next step in the research will be pursuing Investigational New Drug (IND) studies for Gem-miR-129 to establish its safety profile and seek regulatory approval for human clinical trials. This innovative approach is supported by a Veterans Affairs Merit Award and a Stony Brook Cancer Center Pilot Fund.