Researchers at the Spanish National Cancer Research Centre (CNIO) have made a pair of discoveries that could potentially improve the treatment of metastatic brain cancers. In a study led by Dr. Manuel Valiente, the team of researchers found a new biomarker that could indicate whether a patient will respond to radiotherapy. In addition, the study found a drug with the potential to combat resistance to chemotherapy in metastatic brain cancer patients. Following these promising findings, the researchers are planning to conduct clinical studies to determine how effective the biomarker and drug could be in the treatment of cancer in humans.
When Cancer Spreads to the Brain
Cancers from other parts of the body often spread, or metastasize, to the brain, which makes it much more difficult to treat. Patients with solid tumors (common in lung and breast cancers) and melanoma experience metastasis between 20 percent and 40 percent of the time. The majority of these patients lose their lives within a year of discovering that their cancer has spread.
Radiotherapy is one of the most common treatment strategies for cancers that have spread to the brain from other parts of the body. But sadly, tumors in the brain are often resistant to radiotherapy and other forms of treatment. Cancer researchers have been working to understand what causes this resistance and how to prevent it. A better understanding of radiotherapy resistance could eventually lead to more effective treatment methods and, in turn, improved survival rates for those with advanced forms of cancer.
CNIO Research on Radiotherapy Resistance
The CNIO study, recently published in the journal Nature Medicine, analyzed mouse models of brain metastasis. The researchers were specifically looking for a network of proteins within the cancer cells that caused radiotherapy resistance in the cells. Cancer patients donated samples that were then implanted into the mouse models. The researchers discovered that one of the network’s proteins, S100A9, showed a correlation with the response of radiotherapy in metastatic brain cancer patients.
Based on this discovery, the researchers decided to use a simple blood test for detecting levels of S100A9 in a patient’s bloodstream. This test could be used to determine if the patient would be responsive to radiotherapy before implementing the treatment. The CNIO researchers are now in the process of organizing a clinical trial to determine if S100A9 is a predictive biomarker for radiotherapy in cancer patients.
Could RAGE Inhibitors Reverse Radiotherapy Resistance?
In the second part of this study, the CNIO researchers examined whether a type of drug called a receptor for advanced glycation endproducts (RAGE) inhibitor could be used to target the S100A9 mechanism and negate radiotherapy resistance in the mouse models. The drug that the researchers used is safe when administered together with radiotherapy.
Additionally, derivatives of this drug have been tested in phase III clinical trials for other types of brain disorders. The researchers believe that the past trials using similar drugs could expedite the process of testing the RAGE inhibitor in clinical cancer trials. The drug could be combined with the blood test to develop personalized radiotherapy regimens for people who would benefit from taking the drug before treatment.
The Goal of This Study
According to lead author Dr. Valiente, the researchers sought to attempt to understand why radiotherapy is sometimes effective in some parts of the body but not in the brain, as well as how responses could be improved in metastatic brain cancers. Dr. Valiente says the researchers discovered that the brain triggers an inflammatory response that activates a process of strengthening cancer cells when radiotherapy is initiated.
The findings of the study are promising because the researchers may have found an effective way to combat this resistance mechanism through the use of a drug.
Radiotherapy has proven to be an effective cancer treatment in some patients, but its effectiveness has been limited, as not all patients respond to it. Dr. Valiente believes that this study could provide a way to personalize radiotherapy in a way that maximizes its effectiveness based on the unique needs of each patient. Combining radiotherapy with certain drugs could lead to a more sophisticated combination treatment.
The Importance of Personalized Cancer Treatments
Over the past few decades, cancer research has been gravitating toward the development of more personalized treatment methods that address the specific needs of the patient. Oncology researchers believe that the discovery of new personalized treatments could lead to new cures for certain forms of cancer.
The findings of this study have sparked optimism in the oncology community for a new diagnostic test and a new treatment for metastatic brain cancer patients, both of which have the potential to dramatically improve survival rates. The CNIO researchers and others in the oncology research community are optimistic that the clinical trial could eventually lead to new diagnostics, treatments, and prevention methods.