In a proof-of-concept randomized clinical trial conducted by researchers at Weill Cornell Medicine and Angel H. Roffo, treatment with arginine (one of the amino acid components of protein) can improve the effectiveness of radiation therapy for patients with brain metastases Cancer Institute.

The study, published in the journal "Science Advances" on November 5, reported the results of arginine given before standard radiotherapy in 31 patients with brain metastases, which can be administered orally. During the four-year follow-up period, nearly 78% of patients with brain tumors had a complete or partial response, while only 22% of the 32 patients who received a placebo before radiotherapy had such a response.

The test aims to evaluate the effectiveness of arginine as a "radiosensitizer" that enhances the effects of radiotherapy. However, the results and the apparent mechanism of action of arginine indicate that this amino acid may be used more widely as anti-cancer therapy.

"Based on these findings, we should continue to study the combination of arginine with radiotherapy, chemotherapy or immunotherapy, and even the study of arginine itself," said Dr. Leandro Cerchietti, senior author and associate professor of medicine in the Department of Hematology and Medical Oncology, who participated in Trial design and implementation of the Angel H. Roffo Cancer Institute in Argentina, where he is an attending oncologist.

The trial was co-led by Dr. Alfredo Navigante of the Roffo Cancer Institute.

Arginine, also known as L-arginine, is inexpensive and widely available, is generally considered safe, and can enter the brain relatively easily from the blood. The idea of ​​using it to treat cancer stems from the observation that tumors often help their own survival by producing high levels of the related molecule nitric oxide (NO). The latter regulates many processes in the body, including the flow of blood through blood vessels; tumor cells usually produce more nitric oxide by up-regulating the production of a special enzyme called nitric oxide synthase, which is synthesized from arginine Nitric oxide.

Reducing the production of NO is a possible way to exploit the dependence of tumors on this molecule, but the effect is not good, partly because of side effects. The researchers hypothesized that it may be beneficial to promote NO production by adding its precursor arginine, because although tumors can use NO to help their growth and survival, they must keep their production below a certain limit.

"Nitric oxide is a reactive molecule that, by itself or through other reactive molecules derived from it, can cause stress and damage to cells-so the cells can only tolerate so much," the study's lead author Rosette Said Dr. Rossella Marullo. Medical lecturer in the Department of Hematology and Medical Oncology at Weill Cornell Medical College.

She said that overloading high-NO tumors with more NO before radiation therapy may impair the tumor's ability to repair radiation-induced DNA damage. Preclinical experiments in mice confirmed this effect.

In clinical trials, patients received high-dose arginine or a placebo oral suspension to treat brain metastases one hour before radiotherapy-tumors in the brain represent the spread of the primary tumor from other places (such as the lung).

After six months of radiotherapy, 82% of the arginine group's neurological symptoms improved, or at least not worsened, compared to 20% of the placebo group. Most of the arginine-treated patients who died during the study died because the cancer had spread to other parts of the body.

In addition, although metastatic cancer usually has a poor prognosis, there are also cases of patients receiving arginine treatment whose tumors inside and outside the brain have disappeared, indicating the possibility of a cure.

Dr. Cerchietti said that the evidence from this study and previous studies also showed that arginine can not only directly inhibit tumor cells, but also enhance the activity of anti-tumor immune cells.

The promising results prompted the team to start and plan to further study arginine itself or in combination with other anti-cancer treatments.

"In principle, any tumor that overexpresses the NO-producing enzyme is susceptible to arginine treatment-this type of tumor is very common," said Cerchietti, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

He warned that further research is needed and patients should consult their doctor about the use of any supplements outside of clinical trials. The arginine dose used in this study can be used in preparations that can only be obtained in medical institutions.

Jim Schnabel is a freelance writer for Weill Cornell Medicine.

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