In the last 15 years, the IRYCIS aptamer group has worked on the identification and characterization of the MNK1b isoform as well as on the development of aptamers, in collaboration with Aptusbiotech, against this protein as potential antitumor drugs. Thus, an aptamer against MNK1b (apMNKQ2) has been selected and characterized that i) inhibits tumorigenesis, affecting proliferation and the ability to form colonies in three breast tumor lines; ii) produces cell death, mainly through a caspase-mediated apoptotic mechanism; iii) inhibits the metastatic capacity of breast tumor cells by altering the epithelial-mesenchymal transition (EMT) and inhibiting cell migration and invasion. In addition, apMNKQ2 injected intravenously is capable of reducing tumor size, inhibiting tumor cell proliferation and inducing apoptosis in an orthotopic model of triple-negative breast cancer in mice, with the MDA-MB-231 tumor line.
Therefore, with this background and the knowledge that the inhibition of the Mnk-eIF4E pathway sensitizes and increases the efficacy of chemotherapy in CAT, at Aptusbiotech we intend to develop new anti-CAT therapies based on our apMNKQ2, improving its design, developing an alternative RNA molecule and applying updated formulations derived from Nanovex. To that end, Aptusbiotech will test the molecule (and its derivatives and formulations) in cell lines derived from anaplastic thyroid carcinomas. The best-performing combination will continue with preclinical trials using tumors generated in vivo.