News | February 05, 2015

Findings suggest blocking one or more genes might offer effective new treatment for recurrent, treatment-resistant GBM

glioblastoma multiforme, GBM, OSUCCC James, radiation therapy, study

February 5, 2015 — A new study identifies several genes that together enable a lethal form of brain cancer to recur and progress after radiation therapy. The findings might lead to new therapies that target cancer stem cells, say researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), who led the study.

The work focused on the brain cancer glioblastoma multiforme (GBM). It investigated a subset of cancer cells within those tumors that behave like stem cells and that sometimes survive radiation therapy. To understand how those cancer stem-like cells survive irradiation, the researchers examined the cancer-related gene EZH2, which is unregulated in GBM and other cancers.

They discovered that in GBM stem-like cells – but not in other tumor cancer cells or in healthy body cells – EZH2 is regulated by a gene called MELK in combination with a second gene, FOXM1. The interaction of the three genes helps the cells survive therapy.

The findings are published in the journal Stem Cell Reports.

“Currently, GBM is treated surgically followed by radiation therapy and chemotherapy, but these tumors often recur, and patients generally survive less than two years, so we badly need new treatments,” says principal investigator Ichiro Nakano, M.D., Ph.D., associate professor in the division of neurological surgery and a researcher in the OSUCCC – James Translational Therapeutics Program. “Our findings suggest that MELK inhibitors can be applicable to brain and other cancers as a novel cancer stem cell-directed therapy.”

In earlier research, Nakano and his colleagues showed that MELK is highly expressed in glioblastoma stem-like cells, and that over-expression is correlated with poor patient survival.

For this study, Nakano and his colleagues used cells dissociated from GBM tumors, a mouse model and the roundworm Caenorhabditis elegans. Key findings include:

  • MELK and EZH2 proteins occur together in a subset of tumor cells;
  • Without MELK, GBM cells are more sensitive to irradiation; when MELK is restored, the cells become resistant to radiation;
  • Recurrent GBM tumors have higher numbers of MELK- and EZH2-positive cells than newly diagnosed tumors;
  • MELK and the oncogenic transcription factor FOXM1 form a complex that drives EZH2 expression;
  • Levels of MELK, FOXM1 and EZH2 are strongly linked to patient prognosis.

 

“Taken together, our data suggest that MELK upregulation after irradiation promotes radiation resistance, and tumor development and progression,” Nakano says.

For more information: www.cancer.osu.edu


Related Content

News | Oncology Information Management Systems (OIMS)

May 24, 2023 — RaySearch Laboratories AB announced that the oncology information system RayCare* (* subject to ...

Time May 24, 2023
arrow
News | ASTRO

May 23, 2023 — More than 9 in 10 radiation oncologists report that their practices face clinical staff shortages ...

Time May 23, 2023
arrow
News | Radiation Oncology

May 23, 2023 — ZAP Surgical Systems, Inc., a leading innovator in the field of surgical robotics, today announced that ...

Time May 23, 2023
arrow
News | Radiation Oncology

May 22, 2023 — Physicians and scientists from the UCLA Jonsson Comprehensive Cancer Center will discuss the latest ...

Time May 22, 2023
arrow
News | Radiation Therapy

May 15, 2023 — GE HealthCare is presenting three new global innovations – Intelligent Radiation Therapy (iRT), Auto ...

Time May 15, 2023
arrow
News | Artificial Intelligence

May 8, 2023 — Artificial intelligence and machine learning (AI/ML) technologies are constantly finding new applications ...

Time May 08, 2023
arrow
News | Mammography

May 5, 2023 — The American College of Radiology (ACR), Breast Cancer Research Foundation (BCRF) and GE HealthCare ...

Time May 05, 2023
arrow
News | Computed Tomography (CT)

May 5, 2023 — According to an accepted manuscript published in ARRS’ own American Journal of Roentgenology (AJR), a high ...

Time May 05, 2023
arrow
News | Magnetic Resonance Imaging (MRI)

May 2, 2023 — Metabolic disorders are involved in many common health conditions such as Alzheimer's, depression ...

Time May 02, 2023
arrow
News | Radiation Therapy

May 1, 2023 — Prelude Corporation (PreludeDx), a leader in molecular diagnostics and precision medicine for early-stage ...

Time May 01, 2023
arrow
Subscribe Now