Glioblastomas are the most frequent and aggressive brain tumors, with a survival rate that has barely improved in the last 50 years, which highlights, according to the CNIO, the urgent need to develop new therapeutic strategies.

A team of researchers has discovered that a combined drug therapy it could improve the treatment of patients with the most common and aggressive brain tumors, whose survival rate has barely improved in the last fifty years.

The work has been carried out at the National Cancer Research Center (CNIO), where scientists have studied in depth drug resistance – temozolomide – which is used as the main treatment against the most aggressive brain tumor – glioblastoma – in which many of the patients they stop responding over time.

Researchers have found that the combination of this drug with another – dianhydrogalactitol – helps to circumvent these resistance and increases survival, something that they have already shown in mice with brain tumors, as reported by the CNIO on Monday after the publication of the results of this research in the journal Molecular Cancer Therapeutics, from the American Association for Cancer Research.

Glioblastomas are brain tumors more frequent and more aggressive, with a survival rate that has barely improved in the last fifty years, which highlights, the CNIO has underlined, the urgent need to develop new therapeutic strategies.

Pre-clinical work

The team led by the researcher Massimo Squatrito, head of the Brain Tumors Group of the Seve-Ballesteros Foundation of the National Cancer Research Center (CNIO), proposes after his work a novel strategy therapy based on the combination of these two drugs.

Squactel has explained to the EFE agency that it is about a “very encouraging” pre-clinical work, but it has affected that until the results are validated in a clinical setting, it will be difficult to predict when the finding will translate into a beneficial treatment for patients with this type of tumor. “Before our results can have a real impact on patients, this combination has to be proven in clinical trials, to verify their safety and that it will not imply any associated toxicity for them ”, said Squa recently.

The scientist explained that “temozolomide” is already approved for the treatment of glioblastoma, and that the use of “dianhydrogalactitol” is still being investigated in clinical trials and, so far, it has only been approved for the treatment of a type of leukemia and lung cancer in China.

Current treatment

The CNIO has recalled that at present, the main and almost only treatment against this type of brain tumors is the combination of radiation therapy with chemotherapy with “temozolomide”, after surgical removal of the tumor mass.

Like most of the chemotherapies used, this drug damages the genetic material of tumor cells, inducing them to collapse and cell death, and in almost half of the patients the tumors become resistant to this drug and the tumor continues to grow even during treatment.

“Although the incidence of glioblastoma is not excessively high in adults, they are the most frequent brain tumors, for which no effective treatments nor markers of response to treatment or the generation of resistance ”, Squa recently pointed out.

Avoid resistors

But what happens in patients with this type of tumor to stop responding to temozolomide?; The researcher and his team had already shed light on this issue in a previous study, when they found that the tumor managed to grow and avoid treatment.

Now, scientists have studied resistance to temozolomide in depth and have found that tumor cells accumulate mutations that give them the ability to dodge the effects of that drug.

Tumors are complex systems that deploy multiple tools to trick the body and be able to grow and develop, has observed the CNIO; and he has highlighted that one of the great revolutions and hopes for many patients are combined therapies, directed against several of these components that intervene in the tumor process.

Thus, advances in the understanding of the molecular biology of tumors are allowing the emergence of new therapies and their combination in a targeted way to combat them, as well as avoid the resistances that generate. Along these lines, the researchers have focused on “dianhydrogalactitol”, which is already being tested in clinical trials for brain tumors and other types of cancer such as ovarian cancer.

This study has received funding from the Ministry of Science and Innovation, the Carlos III Health Institute, the Seve Ballesteros Foundation, the Spanish Association Against Cancer (AECC) and the European Molecular Biology Organization (EMBO).