Mission
Develop a personalized targeted therapy against
Glioma-initiating Cells for the treatment of Glioblastoma in
combination with the current standard of care.
Brain Tumor
Cancer remains one of the primary causes of human death. Prognosis and therapeutic possibilities vary widely between different types of cancers.
Primary brain tumors (mainly glioma) represent 2% of tumors in adults. In their malignant form (grade IV or or glioblastoma (GB)) remain one of the most aggressive diseases with a 2-year survival of 32% with today’s available standard of care. Worldwide, around 50.000 people are diagnosed with brain tumor every year. Although combining chemotherapy with radiation shows a significant benefit for patients suffering from GB, the mean survival rate remains dismal, 14.6 months on average. The median survival of patients with recurrent (relapsing) GBM treated with the newest available drug Avastin® (bevacizumab) is only of 9.2 months.
Glioma-Initiating Cells (GICs)
A lthough the exact cellular origin of a tumor remains unclear, it is proposed and generally accepted today that a small fraction of cancer cells (<5% of all cancer cells) controls tumor initiation, growth, and recurrence. This fraction of cancer cells represents a unique reservoir of cancer-initiating cells (CICs) (also known as cancer stem cells / CSCs) within the tumor.
The terms CICs and CSCs are commonly used as synonyms.
GICs are specific cells within the brain tumor that cause growth and recurrence of this tumor and that are resistant to standard radio- and chemotherapies. The current challenge resides into identifying and developing efficient therapies against GICs for the treatment of GB and recurrent GB in order to improve the outcome of the patient.
Our mission is to develop a therapy that targets GICs, which are believed to be the resistant “roots” of GB.
This disease represents a high unmet medical need and an attractive niche market for product development.
Technology and in vitro Screening Platforms
Our methodology isolates GICs based on phenotypic rather than molecular criteria without relying on any cell surface marker. It combines the use of three criteria and the use of FACS (Fluorescence-activated cell sorting). The methodology was protected and the know-how kept internally. The technology was validated in more than 98 primary brain tumor tissues, 28 glioma cell cultures and has been translated to non-tumorigenic epileptic tissues and in mouse.
We developed an in vitro screening assay using primary cells from patients. We are therefore able to test and validate the efficacy and specificity of any compound to eradicate GICs in vitro. A total of 13 different marketed and cited compounds (including γ-irradiation, temozolomide, EGFR inhibitors, mTOR inhibitors) were assessed for their ability to eradicate GICs. None of these 13 tested compounds demonstrated the ability to eradicate the GICs in vitro; in all cases, the CICs were able to recover after withdrawal of treatment.
Therapeutic Targets and Molecules
By exploring the biology of the purified GICs and by taking advantage of the developed in vitro screening assay, two novel therapeutic targets were identified, validated and protected. In the last few years, other groups independently confirmed these intracellular targets and their mechanism of action. Three mother molecules demonstrated an exceptional ability to eradicate the GIC population with low effects on non-tumorigenic brain cells and cancer cells. It is important to note that 2 of the compounds are commercially available molecules and the 3rd one is an approved drug. In order to create composition of matter patent protection, a small biochemistry program was initiated in collaboration with the ETH Zürich. This collaboration has allowed the protection and synthetization of novel family compounds, all derived from the mother molecule. 1 HIT-compound was selected to generate more derivatives with the ultimate goal to select hit-to-lead candidates. At present, 5 current lead molecules have been identified.
Contact:
Virginie Clément-Schatlo, PhD
D-37085 Göttingen
Germany
Cell: +49 157 313 54 551
Email: vcs@glitther.de