One of the most remarkable features of glioblastoma is the metabolic reprogramming of cancerous cells, resulting in uncontrolled cell proliferation, hypoxic conditions and angiogenesis. Metabolic reprogramming enables tumor cells with a faster way to produce energy and form new membranes. For this and other reasons, glioblastoma is presently incurable and the affected patients have a poor outcome.
One of the possible strategies for defeating brain tumors is to interfere with the pathways of nutrient supply. This may be achieved by blocking the utilization routes of glucose or lipids.
In a new study published in the Journal of Cellular Physiology, researchers examined the effects of a new inhibitor, AA452, of a transcription factor, PPARα, known to be involved in the control of energetic metabolism. The result obtained in this study indicates that blocking PPARα in glioblastoma cells affected a strong decrease of cell proliferation and migration, as well as induced a major sensitivity to radiotherapy.
The research is a collaboration from the Sbarro Health Research Organization (SHRO, Center for Biotechnology, Temple University, Philadelphia PA USA), the University of L’Aquila (Italy) and University of Siena (Italy).
This finding may have important implications for the design of new drugs and therapeutic interventions for this incurable tumor.
“Our studies point towards a possible way to counteract glioblastoma growth and recurrence by interfering with energetic metabolism by blocking PPARα,” says Annamaria Cimini of the University of L’Aquila, lead author of the study.
“The design of a new drug specifically directed against PPARα activity may provide new perspectives for glioblastoma therapies by counteracting its energy supply,” says Antonio Giordano, founder and director of the Sbarro Institute for Cancer Research and Molecular Medicine.