Nat Commun: Dual target polyamine synthesis and ingestion: a potential treatment strategy for diffuse endogenetic brain bridge glioma

Diffuse endogenetic cerebral bridge glioma (DIPG) is an incurable and invasive malignant brain tumor with a medium survival of less than one year and a five-year survival rate of less than 1%, making it the most common high-level glioma in children.
the disease is fatal, there is no effective treatment, and is still the main cause of childhood brain tumor-related deaths.
although more than 250 clinical trials have been conducted on the disease using different treatment strategies, the adverse prognosis of DIPG has not improved and topical radiotherapy remains the standard treatment strategy for the disease.
previous studies have shown that the development of new therapies with low toxicity and the ability to cross the blood-brain barrier will provide new treatment options for DIPG patients. polyamine synthesis and metabolic gene polyamines in
brain tumors are small organic cation polymers that play a vital role in a variety of cellular processes, including DNA replication, translation, and cell proliferation, so there are many studies exploring their function in invasive tumors.
ODC1 (birdine dehydrase 1) is a speed-limiting enzyme in polyamine synthesis and can be irreversibly inhibited by DFMO (teflone methylphenidate).
analysis of the efficacy of DFMO and AMXT 1501 combined therapy in this study, the researchers found that the synthesis of polyamines in DIPG was increased and led to an increase in DFMO sensitivity.
studies have shown that DIPG cells can compensate for the inhibition of ODC1 by raising the expression of the polyamine transport protein SLC3A2.
Treatment with the polyamine transport protein inhibitor AMXT 1501 can reduce the intake of DIPG cells to polyamines, and the combined dosage of AMXT 1501 and DFMO can produce effective in vitro activity and show significant life-prolonging effect in three invasive DIPG in-place animal models.
, these results demonstrate a potential therapeutic strategy for dual-target polyamine synthesis and ingestion or diPG.