Dipg-04. Combined Targeting of Calcium Signalling and RTK/Pi3k Pathway Is A novel Therapeutic Approach Against Diffuse Intrinsic Pontine Glioma

Abstract

NEURO-ONCOLOGY • JUNE 2017chemotherapy -and observation only. The parents elected careful follow-up. Now 16 months following biopsy, the child is developing well and the MRI is stable, with advanced imaging characteristics of a low-grade glial lesion. Case 2. A male was diagnosed in utero with hydrocephalus, a post-natal MRI confirming this and revealing a small tectal mass. An ETV and biopsy were performed, yielding a tiny tumor fragment; pathology was consistent with a diffuse glial tumor, with rare mitoses; IDH1 and ATRX intact, P53 negative, GFAP positive and Ki67 20-30%. The tumor was deemed a highgrade glioma. Insufficient tissue for sequencing was available. The infant has been followed with close follow-up MRI scans with advanced imaging, which remain consistent with a low-grade glioma, and continues stable at 3 months since birth; a repeat biopsy is planned concomitant with shunt revision. CONCLUSION: Infants with tectal gliomas are rare, and anecdotally never undergo progression to high-grade. In the absence of definitive sequencing data, extreme caution should be exercised in offering treatment recommendations.

A pilot radiogenomic study of DIPG reveals distinct subgroups with unique clinical trajectories and therapeutic targets

“…These findings are in agreement with research by Shen et al demonstrating that pediatric high-grade gliomas undergo metabolic reprogramming, favoring glycolysis over oxidative phosphorylation, and therefore shifting glucose metabolism to mitochondrial oxidation represents a potential therapeutic target [67]. Additionally, our results are consistent with prior work by Deng et al suggesting downregulated genes related to calcium signaling may be a key mechanism in the development and progression of DIPG [18], and potentially targetable via a combination of calcineurin and receptor tyrosine kinase/PI3K pathway inhibition [70].…”