Research reveals protein ADAR1 as new therapeutic target to treat brain cancer

Research has revealed a new mechanism within cancer cells that could be exploited to treat glioblastoma—one of the deadliest types of brain tumors.

Dr. Ángel Álvarez-Prado, one of The Brain Tumor Charity’s Future Leaders and a postdoctoral researcher at the University of Lausanne in Switzerland, discovered that blocking a protein called ADAR1 had a two-fold effect on glioblastoma tumors.

Firstly, it reduced the ability of cancer cells to multiply and then—crucially, kicked the immune system into action to recognize and attack the tumor.

His findings, published in Cell Reports, establish the therapeutic potential of targeting ADAR1 in glioblastoma.

Dr. Álvarez-Prado, who has gone on to run his own laboratory at the Luxembourg Institute of Health, is now evaluating different ADAR1-inhibiting drugs with the long-term goal of improving patient care.

If his team’s findings in the laboratory can be replicated in clinical trials, it could lead to the development of more effective therapies against this aggressive disease—the first advance in treatment for glioblastoma since 2007.

About 3,200 people are diagnosed with glioblastoma (GBM) in the U.K. every year, and standard treatment involves surgery, radiotherapy and/or temozolomide chemotherapy. But these treatments don’t usually cure the condition and there are side effects. People live, on average, for just 12–18 months after they are diagnosed.

While this research is still at a relatively early stage, The Brain Tumor Charity continues to support Dr. Ángel Álvarez-Prado and his new team to help drive this vital work nearer to the clinic.

Dr. Simon Newman, Chief Scientific Officer at The Brain Tumor Charity, said, “Identifying weaknesses in tumor cells, allowing scientists to both directly target the cancer cells and train our immune system to recognize them, is a powerful way to develop urgently needed treatments.

“We are immensely impressed by and proud of the work Ángel has achieved here. He is one of our Future Leaders—a group of the brightest early-career neuro-oncology researchers whose work we are supporting—and we look forward to his career flourishing to help drive exciting discoveries like these nearer to the clinic.”

Dr. Álvarez-Prado said, “Glioblastomas present a huge challenge. They are very complex and aggressive cancers, and we urgently need new treatments for patients.

“We wanted to see if blocking ADAR1—a protein normally involved in anti-viral immunity—in mice with glioblastoma tumors would affect tumor growth. We discovered that tumors grew more slowly, the immune system became active and fought the cancer, and mice survived for longer. Blocking ADAR1 in human glioblastoma cells also reduced the ability of cancer cells to multiply.

“Our work has revealed a potential treatment avenue to explore. My laboratory is now searching for and evaluating different drugs to block ADAR1 function. This is a critical step in identifying relevant molecules that can subsequently be tested in clinical trials and, hopefully, result in a more effective therapy for patients with glioblastoma.”

Provided by
The Brain Tumour Charity

Research has revealed a new mechanism within cancer cells that could be exploited to treat glioblastoma—one of the deadliest types of brain tumors.

Dr. Ángel Álvarez-Prado, one of The Brain Tumor Charity’s Future Leaders and a postdoctoral researcher at the University of Lausanne in Switzerland, discovered that blocking a protein called ADAR1 had a two-fold effect on glioblastoma tumors.

Firstly, it reduced the ability of cancer cells to multiply and then—crucially, kicked the immune system into action to recognize and attack the tumor.

His findings, published in Cell Reports, establish the therapeutic potential of targeting ADAR1 in glioblastoma.

Dr. Álvarez-Prado, who has gone on to run his own laboratory at the Luxembourg Institute of Health, is now evaluating different ADAR1-inhibiting drugs with the long-term goal of improving patient care.

If his team’s findings in the laboratory can be replicated in clinical trials, it could lead to the development of more effective therapies against this aggressive disease—the first advance in treatment for glioblastoma since 2007.

About 3,200 people are diagnosed with glioblastoma (GBM) in the U.K. every year, and standard treatment involves surgery, radiotherapy and/or temozolomide chemotherapy. But these treatments don’t usually cure the condition and there are side effects. People live, on average, for just 12–18 months after they are diagnosed.

While this research is still at a relatively early stage, The Brain Tumor Charity continues to support Dr. Ángel Álvarez-Prado and his new team to help drive this vital work nearer to the clinic.

Dr. Simon Newman, Chief Scientific Officer at The Brain Tumor Charity, said, “Identifying weaknesses in tumor cells, allowing scientists to both directly target the cancer cells and train our immune system to recognize them, is a powerful way to develop urgently needed treatments.

“We are immensely impressed by and proud of the work Ángel has achieved here. He is one of our Future Leaders—a group of the brightest early-career neuro-oncology researchers whose work we are supporting—and we look forward to his career flourishing to help drive exciting discoveries like these nearer to the clinic.”

Dr. Álvarez-Prado said, “Glioblastomas present a huge challenge. They are very complex and aggressive cancers, and we urgently need new treatments for patients.

“We wanted to see if blocking ADAR1—a protein normally involved in anti-viral immunity—in mice with glioblastoma tumors would affect tumor growth. We discovered that tumors grew more slowly, the immune system became active and fought the cancer, and mice survived for longer. Blocking ADAR1 in human glioblastoma cells also reduced the ability of cancer cells to multiply.

“Our work has revealed a potential treatment avenue to explore. My laboratory is now searching for and evaluating different drugs to block ADAR1 function. This is a critical step in identifying relevant molecules that can subsequently be tested in clinical trials and, hopefully, result in a more effective therapy for patients with glioblastoma.”

Provided by
The Brain Tumour Charity