methotrexate + 5-fluorouracil + gemcitabine + microRNA-15a

MTX-5FU-Gem-miR-15a is a novel, multi-component nucleic acid-based therapeutic developed by Stony Brook University (SUNY) as a multimodal strategy for cancer treatment. The drug is a chemically modified microRNA-15a (miR-15a) mimic in which uracil residues are replaced with the antimetabolite 5-fluorouracil (5-FU), and the construct is further conjugated with methotrexate (MTX) and gemcitabine (Gem). This design allows the molecule to act as a tumor suppressor by targeting key proteins such as WEE1, CHK1, YAP1, BCL2, BMI1, and DCLK1, while the integrated chemotherapeutic agents provide synergistic disruption of DNA repair and synthesis. Methotrexate serves a dual role by inhibiting dihydrofolate reductase and enhancing tumor cell specificity via folate receptor targeting. Preclinical studies in epithelial ovarian cancer (EOC) models, including those resistant to PARP inhibitors like olaparib, have shown that MTX-5FU-Gem-miR-15a can significantly reduce tumor burden and overcome drug resistance without the need for a delivery vehicle. It is also being investigated for pancreatic ductal adenocarcinoma and colorectal cancer.

Other names

MTX-5FU-Gem-miR-15aMTX5FU-Gem-miR-15aMTX 5FU-Gem-miR-15aMTX-5-FU-Gem-miR-15aMTX5-FU-Gem-miR-15aMTX 5-FU-Gem-miR-15a