Glioblastoma is the most aggressive brain cancer. Each year it causes more than 200,000 deaths worldwide and the average life expectancy of patients is less than two years. This cancer gives few life options to patients who suffer from it, points out Nabil Hajji, from Imperial College London, UK, whose team seems to have found a new approach not only to increase life expectancy, but also to cure patients.
The strategy seems simple: starve tumor cells.
The researchers have used a drug -ADI-PEG20- capable of degrading arginine in the blood of the systemic circulation. Arginine, he explains, “is a semi-essential amino acid that is normally
found in the diet, but required by a variety of cancer cells, especially those that grow rapidly; Thus, depriving tumors of this amino acid has been explored as a possible anticancer strategy in a variety of tumor typesincluding glioblastoma.
Our study, published in the “Journal Of Clinical Investigation”, in which researchers from the University of Seville have also participated, used this drug with the aim of depriving tumors of arginine and reducing their growth, thus overcoming the difficulties that represents the blood-brain barrier.
In preclinical trials, notes Nabil Hajji, the use of the drug in combination with radiotherapy, «has been able to completely eliminate the brain tumor». This effect, he explains, is due «mainly to the reactivation of the immune system, especially microglial cells».
Microglia are the resident macrophage population of the central nervous system (CNS) and one of their most representative functions is their phagocytic activity (which means ‘eat cells‘), presenting an effective role in cleaning normally damaged cell debris and preventing inflammation in brain tissue.
It is known, explains this researcher, that in glioblastomas the microglia infiltrate and together form a large part of the tumor microenvironment that contributes up to 30% of the tumor mass. “The question we had before starting this research was why can’t microglia attack the tumor by exerting their phagocytic activity?”
In their work, by depriving arginine from the systemic blood as a pretreatment, “we have managed to change the polarity of the microglia to an antitumor inflammatory phenotype with a very high phagocytic capacity. The use of radiotherapy then manages to cure animals with aggressive and terminal brain tumors with total survival of all treated animals and no apparent toxicity.’
The researchers have already designed a phase I clinical trial to test their results. However, there is already a clinical trial with a small number of patients (32) with glioblastoma that examined the use of the same drug, “and its results are very promising and without toxic side effects.”
The drug used in turn regulates the metabolism of arginine and takes advantage of the most common epigenetic alterations in patients with glioblastoma to increase sensitivity to conventional treatments.
Because unfortunately, he comments, today the survival of patients can only be improved with the advances made, but they are not enough.
“Many preclinical studies look promising; but when they are applied or tested in the clinic, they don’t work”, recognizes the researcher for whom the future passes through precision medicine.
“Identifying the genetic, epigenetic and metabolic abnormalities of the tumors and of each patient together with bioinformatics will help to understand this type of cancer and finally select the appropriate and personalized treatment regimen for each patient,” he points out.
In this sense, he states, «at KeyZell, a biotechnological startup of which I am a co-founder, we are working on an innovative tool assisted by Artificial Intelligence, called Oncology Precisión System, which is capable of, based on a large amount of input data (such as genomic information, clinical history and approved treatments) recognizing patterns to offer a diagnostic value or a prognostic value and to be able to personalize a treatment or a combination of drugs for each patient. This system created from KeyZell aims to be the future of precision medicine in oncology.”
And he adds that, in the long term, “it is important to highlight that the future in the treatment of glioblastoma lies in non-invasive therapies, such as focused ultrasound (FUS), which is a non-invasive therapeutic technology with the potential to improve the treatment of glioblastoma. glioblastoma”, which is already “being applied in clinical trials and has been used for pediatric brain cancer with good results and will soon be generalized for adults. This approach uses lower levels of energy to break the blood-brain barrier and can transiently open the blood-brain barrier to chemotherapy, allowing efficient treatment of glioblastoma tumors.».