Eukaryotic Translation Initiation Factors (eIFs) as novel biomarkers in bladder cancer and in head and neck squamous cell carcinoma
Prof. Dr Christoph Arens, Otto von Guericke University Magdeburg; Anna Maria Cyran, Otto von Guericke University Magdeburg; Prof. Dr Johannes Haybäck, Otto von Guericke University Magdeburg; Prof. Dr Michael Naumann, Otto von Guericke University Magdeburg; Jeton Luzha, Otto von Guericke University Magdeburg
Otto von Guericke University Magdeburg, Transfer and Entrepreneur Centre
Bladder cancer is the second most common genitourinary malignancy and represents the 9th most common cancer worldwide. Urinary bladder cancer (UBC) is the most common histology of bladder cancer and is associated with high mortality rates and poor prognosis. Painless hematuria and other signs and symptoms of UBC are not specific and often arise at late stage of disease. Thus, diagnosis is typically made when the cancer is already in advanced stages and prognosis for survival is bad. Head and Neck Squamous Cell Carcinoma (HNSCC) develops in the mucosa of the oral cavity of the pharynx, larynx and paranasal sinuses. Every year over 68 000 patients are diagnosed new with HNSCC worldwide. The mortality rate is estimated at 40-50 %. HNSCC is characterized by extraordinary intratumoral and intertumoral genetic heterogeneity, which might explain the different reactions of patients to HNSCC therapy. This underlines the need to provide therapies for the treatment of HNSCC.
The inventors examined the performance of eukaryotic translation initiation factors (eIFs) as biomarkers in bladder cancer and in Head and Neck Squamous Cell Carcinoma. They ascertained that eIFs represent crossroads in the development of bladder cancer and can serve as biomarkers for bladder cancer. In particular, the present inventors found that eIFs are deregulated between patients suffering from UBC and healthy individuals. They identified eIF1, eIF5a, EIF4B, eIF4G, eIF5B, eIF6 and eIF3H as new diagnostic biomarkers for urinary bladder cancer. These new diagnostic biomarkers allow the diagnosis and monitoring of UBC. Furthermore, the inventors examined the mRNA expression data of 279 HNSCC patients and found that patients with high expression of all subunits of eIF2 and low expression of the eIF2AK1/HRI kinase showed a lower overall survival. Further, they found that upregulation of all subunits of eIF2 and downregulation of eIF2AK1/HRI compared to healthy controls is indicative for HNSCC. The inventors also found that the treatment with eIF2S1/eIF2α inhibitor Salubrinal leads to a reduction of cell viability in vitro and in 3D organoids experiments. Thus eIF2α eIF is useful both as a molecular marker and as a therapeutic target in HNSCC.
We offer licensing opportunities for the invention and the biomarkers.
Experiments for the validation were successfully performed.
Two European patents were filed:
EP 10 170 329.7
EP 19 187 871.9