Glioblastoma is a serious and incurable brain cancer. Patients who receive this diagnosis typically have 11-20 months to live. One of the main difficulties in treating this cancer is that its cells quickly build up a resistance to chemotherapy. In the upcoming issue of Nucleic Acids Research, Professor Rotem Karni and his team at the Hebrew University of Jerusalem’s Institute for Medical Research share promising results for a new glioblastoma treatment with the potential to improve and extend patients’ lives.

As part of their research, Karni and Ph.D. student Maxim Mogilevsky designed a molecule that inhibits glioblastoma tumor growth by regulating the proteins it produces. The MKNK2 gene produces two different protein products through a process called “RNA alternative splicing.” These proteins have two opposing functions: MNK2a inhibits cancer growth, whereas MNK2b supports cancer growth. Karni’s new molecule shifts the splicing of MKNK2 so that production of the tumor-stimulating protein decreases, while production of the tumor-suppressing protein increases. As a result, cancerous tumors decrease or die-off completely.

HU Professor Rotem Karni and Ph.D. student Maxim Mogilevsky in the lab

“Not only can this breakthrough molecule kill tumor cells on its own, but it also has the power to help former chemotherapy-resistant cells become chemotherapy-sensitive once again,” shared Professor Karni.

In his study, the biological models with human glioblastoma tumor cells that were treated with this new molecule saw their tumors shrink or die off completely, as opposed to the control biological models who were treated with an inactive molecule. “Our research presents a novel approach for glioblastoma treatment. In the future, we’ll be able to tailor treatments for patients based on the amount of cancer-inhibiting proteins that their tumors produce,” added Karni.

A patent for this technology has been registered and granted in the United States and Europe through Yissum, Hebrew University’s R&D company.

CITATION: Modulation of MKNK2 alternative splicing by splice-switching oligonucleotides as a novel approach for glioblastoma treatment. Maxim Mogilevsky, Odelia Shimshon, Saran Kumar, Adi Mogilevsky, Eli Keshet, Eylon Yavin, Florian Heyd, and Rotem Karni. DOI: https://doi.org/10.1093/nar/gky921

FUNDING: German-Israel Foundation, Israel Innovation Authority, Israel Science Foundation, Israel Cancer Research Fund, Israel Cancer Association, The Henry & Merilyn Taub Foundation, and the Carol Epstein Foundation.