Pretreatment with pharmacologic doses of oral L-arginine enhances the effect of radiation therapy in patients with unresectable brain metastases related to solid tumors, according to a study published in Science Advances. This allows greater local control of the disease and could provide an affordable way to optimize the effect of radiation, or even other treatments, on primary or metastatic tumors.
L-arginine, commonly used as a supplement for erectile dysfunction or lack of sexual desire, is a substrate of the nitric oxide synthase enzyme, which produces nitric oxide in tissue. Nitric oxide is a gas that has been shown, in relatively high concentrations, to induce chemo- and radiosensitization in preclinical models and in patients with solid tumors.
These study demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate L-arginine decreases tumor lactate in BM patients. In a placebo- controlled trial, showed that administration of L-arginine before each fraction enhanced the effect of radiation, improving the control of BM. Studies in preclinical models demonstrated that L-arginine radiosensitization is a NO-mediated mechanism secondary to the metabolic adaptation induced in cancer cells.
Researcher showed that the decrease in tumor lactate was a consequence of reduced glycolysis that also impacted ATP and NAD+ levels. These effects were associated with NO-dependent inhibition of GAPDH and hyperactivation of PARP upon nitrosative DNA damage. These metabolic changes ultimately impaired the repair of DNA damage induced by radiation in cancer cells while greatly sparing tumor-infiltrating lymphocyte
Image: Illustration (source: https://www.ncbi.nlm.nih.gov/)
Reference:
1. Rossella Marullo, Monica Castro, Shira Yomtoubian, M. Nieves Calvo-Vidal, Maria Victoria Revuelta, Jan Krumsiek, Andrew Cho, Pablo Cresta Morgado, Shao Ning Yang, Vanina Medina, Berta M. Roth, Marcelo Bonomi, Kayvan R. Keshari, Vivek Mittal, Alfredo Navigante, Leandro Cerchiett. The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases. Internet [Cited 18/11/2021]. Available from: https://www.science.org/doi/10.1126/sciadv.abg1964
2. Matías A. Loewy. L-arginine Enhances Effect of Radiation on Brain Metastases. https://www.medscape.com/viewarticle/963158#vp_1
