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.

Thyroid cancer is a common malignancy of the endocrine system. Thyroid cancer is a common malignancy of the endocrine system. Among the various types of thyroid carcinoma, anaplastic thyroid carcinoma (CAT) is the most aggressive and lethal histologic type with a median survival of 3-9 months. It accounts for less than 2% of thyroid cancers and affects adult patients between the sixth and eighth decade of life. The usual clinical picture is a rapidly growing thyroid mass invading surrounding structures with compressive symptoms. It is often accompanied by cervical lymph node enlargement and distant metastasis.

The clinical management of CAT is challenging as it is highly resistant to chemotherapy. The treatment regimen combines surgery, when feasible, accelerated hyperfractionated external beam radiotherapy and doxorubicin-based chemotherapy. This treatment can provide locoregional control of disease, but does not affect overall survival in patients with distant metastases. Therapeutic research is studying different redifferentiation strategies and target therapies for the inhibition of EGF receptors and neoplastic angiogenesis.

The molecular mechanisms leading to the development and progression of CAT are complex and not yet fully understood, although they are known to involve activation of the MAPK pathway, AKT/mTOR and Wnt-ß-catenin. However, the underlying mechanisms of ATC resistance to chemotherapy are not well understood.

Protein synthesis plays an important role in regulating gene expression and dysregulation of eIF4E contributes to aberrant proliferation and survival in cancer. elF4E-regulated protein synthesis in cancer cells has been described as playing an essential role in chemotherapy resistance. Overexpression of eIF4E and MAPK-interacting kinase (Mnk)-kinase correlates with poor cancer prognosis as it preferentially enhances the translation of carcinogenesis-associated mRNAs.