New study finds way to improve how radiotherapy is used for people with cancer that has spread to the brain (High S100A9 protein level needs a RAGE inhibitor, low S100A9 works well with normal radiotherapy)

Medical Xpress / Worldwide Cancer Research / Nature Medicine ^ | Apr. 11, 2022 | Manuel Valiente et al

[ConservativeMind]

Researchers have uncovered how cancer cells that have spread to the brain (metastasis) are able to resist the effects of radiotherapy. The study reveals a new biomarker detected in a blood test to indicate whether a patient will respond to radiotherapy. The researchers also discovered a specific type of drug, called a RAGE inhibitor, which can enter the brain and reverse the resistance to radiotherapy.

Radiotherapy is considered the gold standard treatment for tumors that have spread to the brain from elsewhere in the body, but these tumors are resistant to treatment in many cases.

The researchers discovered that one protein, called S100A9, correlated with how well people with brain metastasis respond to radiotherapy. A simple blood test could detect levels of S100A9 and determine if a patient will respond to radiotherapy before treatment begins.

The study also discovered that a RAGE inhibitor can target the newly discovered mechanism and reverse resistance to radiotherapy in mouse models. The drug used in this study is known to be safe when combined with radiotherapy and there are derivatives of it that have been used in phase III clinical trials for other brain disorders. Combining the blood test with the new drug could help personalize radiotherapy by identifying people who would benefit from the drug prior to treatment.

Dr. Manuel Valiente, lead author, says that they "set out to try and understand why radiotherapy can sometimes work in other parts of the body but not in the brain, and see if we could improve responses in patients with brain metastasis. We discovered that the brain activates an inflammatory response that unintentionally triggers a process that makes cancer cells stronger when receiving radiotherapy. Luckily, we also found an Achilles heel of this resistance mechanism and learned how to block it with a drug."

[ConservativeMind]

Two RAGE inhibitors were called out in the study (FPS-ZM1 and azeliragon (TTP488), and these are on limited availability for use in the US. Specifically, the study used FPS-ZM1 for its results.

What should be more available is testing for the S100A9 protein. A test for its level could prevent what might be an ineffective series of radiation doses on the brain.

[ConservativeMind]

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