Molecular techniques are really just a way to manipulate the body and are at their best when they can be utilized to improve health outcomes and save lives.
Recently, a paper came out in Brain, the Oxford Academic Journal of Neuroscience, on manipulating the mTORC pathway to induce cell death in glioblastomas. Glioblastomas are an aggressive type of cancer with a poor prognosis. While there are some drugs to treat it on first exposure, nobody knows how to deal with it when it returns. Unfortunately, this disease is highly prone to recur and cause death.
This paper addresses the mTORC pathway and possible therapeutic routes of treatment for glioblastomas. EGFR, which the authors have previously shown to inhibit the mTORC pathway, has made glioblastomas more resilient to hypoxic, or low oxygen conditions. Thus, the authors believed that cranking up activation on mTORC pathway and causing hypoxia in glioblastomas, might be an effective way to kill these cancer cells.
Effectively, they target TSC2sh, an inhibitor of a pathway, and downregulate the repressor. Doing so yields a total increase in activation of glioblastomas, increasing expression of mTORC and causing hypoxic conditions. Mitochondrial genes are upregulated, PPARGC1A and PPARGC1B, and an increase in oxygen usage was observed in said cells.
This has future implications in the treatment for glioblastomas and may perhaps signal a new status quo in treatment for certain cohorts afflicted with the disease.
- Anna-Luisa Thiepold, Nadja I. Lorenz, Martha Foltyn, Anna L. Engel, Iris Divé, Hans Urban, Sonja Heller, Ines Bruns, Ute Hofmann, Stefan Dröse, Patrick N. Harter, Michel Mittelbronn, Joachim P. Steinbach, Michael W. Ronellenfitsch; Mammalian target of rapamycin complex 1 activation sensitizes human glioma cells to hypoxia-induced cell death, Brain, Volume 140, Issue 10, 1 October 2017, Pages 2623–2638, https://doi.org/10.1093/brain/awx196