Granted patent in Europe (EP3494228B1)
Patent application filed in the United States (US20200181713A1)
Patent published worldwide (WO2018024609A2)
Priority date: August 3rd, 2016
Patent application filed in Europe (EP3494218A2)
and the United States (US20210054374A1)
Patent published worldwide (WO2018024608A2)
Priority date: August 3rd, 2016
Eukaryotic translation initiation factors (eIFs) are crucial in the initiation of protein translation. Protein biosynthesis can directly target the translation of specific mRNA and foster cell viability, invasion, formation of metastasis and tumor proliferation. Deregulated protein biosynthesis contributes to carcinogenesis and the progression of cancer.
eIFs have been described to be aberrantly expressed in various tumor entities, showing association with tumor development and cancer progression.
Influence of eukaryotic translation initiation factor 6 (eIF6) on non-small lung cancer development and progression.
Gantenbein et al., 2018, EJC
This patent covers methods for prognosing and diagnosing hepatocellular carcinoma (HCC) and lymphoma. HCC is the most common type of primary liver cancer and the third leading cause of cancer-related deaths worldwide. Furthermore, hepatitis C and hepatitis B infection can induce HCC.
Lymphoma is a group of blood cell tumors that develop from lymphocytes. The diffuse large B-cell lymphoma is most frequent in adults, and 40% of patients are not cured due to the heterogeneity of the disease.
We investigated the relevance of eIFs in HCC and lymphoma and analyzed their prognostic properties. We showed the relationship between the aberrant expression of various eIFs and patient outcome. The established method includes the diagnosis of non-virus-related HCC, hepatitis C- and hepatitis B-associated HCC by determining the expression level of at least one eIF in patient samples.
elF expression in liver metastases of CC and RC compared to NNLT. (A) Representative pictures of immunohistochemical stainings from liver metasteses of primary CRC. Scale bars: 200um and 50um. (B) Densitometric analysis of immunohistochemical staining from various elF subunits in liver metasteses of primary CC (CC- Met) and RC (RC-Met) compared to non-neoplastic liver tissues (NNLT).
Given the poor methods prognosing HCC available so far, we provide a better prognosis and diagnosis with eIF biomarkers for non-virus related and virus related HCCs.
By determining the expression levels of eIFs in lymphoma affected patients, a better prognosis for the patient and decision support for the treatment can be made. High-risk patients can be supervised after treatment to prevent a disease relapse.
In most cases, tumors are currently treated by using chemotherapies, antibodies and further substance classes. Additionally, solid tumors are regularly treated using surgical methods. However, chemotherapeutics may be used only for specific tumor types and/or can cause various side effects.
With this patent, we provide a new approach to treat tumors using eIFs as targets. We consider eIFs as antitumor compounds and as tool for tumor diagnosis in CRC (especially separation in colon and rectal cancer), lung cancer, cholangiocellular carcinoma, pancreatic cancer, hepatocellular carcinoma, lymphoma and glioma.
We have explored the role of currently known eIFs in lung cancer, colorectal cancer and glioma, amongst others. We were able to identify a causal relationship between aberrant eIF expression and tumor development and showed that eIFs play a potential role as novel prognostic and predictive biomarkers as well as anti-tumorigenic approaches.
Basic characterization of various eukaryotic initiation factors (eIFs) for protein level in astrocytomas (WHO grades I-IV) compared to CCBT.
eIF protein expression was analzyed using immunoblot analysis. Representative immunoblots for eIF5, eIF6, (p-) eIF2alpha, eIF1A, eIF3 subunits (A, B, C, D, H, I, J, M), eIF4F complex members (4A1, 4E, (p-)4G), eIF4H and IDH1 (R132H) are shown.
eIFs are promising targets for several tumor entities and could be used in cancer therapy and as potential prognostic biomarkers. Especially for glioma, the standard of care after tumor diagnosis did not change in the previous years, thus novel biomarkers for reliable prognosis, tumor diagnosis, monitoring of the course of cancer and determination of a treatment response are of high importance.
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