Understanding the Deadly Silence of Posterior Fossa A Ependymoma

Abstract

In a breakthrough study in a recent issue of Cell, Michealraj et al. (2020) demonstrate that posterior fossa A ependymoma, a lethal pediatric brain tumor with a silent genome, is dependent upon metabolic changes associated with hypoxia that drive the tumor's characteristic epigenetic dysregulation.

Hallmarks of Cancer: New Dimensions

“…Like many embryonic and pediatric tumors, this form lacks recurrent mutations, in particular a dearth of driver mutations in oncogenes and tumor suppressors. Rather, the aberrant growth of these cancer cells is demonstrably governed by a gene regulatory program induced by hypoxia (60,61). Notably, the putative cell-of-origin of this cancer resides in a hypoxic compartment, likely sensitizing cells resident therein to the initiation of tumorigenesis by as yet unknown cofactors.…”

Benzo[d]isoxazole Derivatives as Hypoxia-Inducible Factor (HIF)-1α Inhibitors

“…Hanahan recently concluded new dimensions of cancer hallmarks in 2022 in that the tumor microenvironment can cause broad epigenetic changes . Hypoxia is a main characteristic in the tumor microenvironment due to a lack of vascularization, which can influence and alter the methylome as well as translational control and thus cause aberrant growth. , As a transcriptional factor, hypoxia-inducible factor (HIF) is what cells mainly depend on to adapt to a hypoxia environment and plays a significant role in regulating VEGF via binding to the HRE (hypoxic response element). The upregulated VEGF can thus promote tumor vascularization and progression …”