HYPOTHESIS: DOES ＂AUTOPHAGY PARADOX＂ STRATEGY TO STANDARD THERAPY OF GLIOBLASTOMA MULTIFORME GAIN BENEFIT?

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. Combined surgery, adjuvant radiotherapy (RT), and temozolomide (TMZ) is the standard treatment of care, but the outcome is still grave. Thus, novel therapeutic targets are actively researched in translational studies. Modulation of autophagy by simultaneous administration of the inducer, sirolimus (Rapamycin), and the inhibitor, hydroxychloroquine (HCQ), breaks the vicious cycle of energy supply from the tumor microenvironment (TME) to cancer cells. This strategy was called the ＂autophagy paradox＂. It has been applied to a variety of cancers to reverse drug resistance. A line of evidences including GBM are characterized by low autophagy capacity and highly dependent on the help of TME to provide energy source and biochemical building blocks for tumor growth and survival. Based on literature review and our experience, we hypothesize that add-on ＂autophagy paradox＂ strategy to standard RT-TMZ will be advantageous to GBM treatment.

關鍵字

Glioblastoma multiforme ； Radiotherapy ； Rapamycin ； Hydroxychloroquine ； Autophagy

並列摘要

多形性膠質母細胞瘤（GBM）是最惡性的原發腦瘤。目前的標準治療為手術加上輔助性的放射及化學治療（temozolomide），然而此疾病預後仍是極差。有鑑於此，各式新型的藥物治療乃蓬勃發展。同時加上促進自噬作用的藥物：sirolimus（Rapamycin），與其抑制藥物hydroxychloroquine（HCQ, CQ）可以破壞癌症細胞從腫瘤微環境獲取能量的平衡。這個治療策略被稱為“自噬作用的悖論”。此方法已經在不同的癌症發現有逆轉藥物抗藥性的效果。細胞實驗發現GBM自噬作用不高，因而需要大量依賴腫瘤微環境供給能量成長。根據文獻探索與臨床經驗，我們假設在傳統化放療加上自噬作用調控的藥物對於多形性膠質母細胞瘤的治療是有助益的。

並列關鍵字

多形性膠質母細胞瘤；放射治療； Rapamycin ； Hydroxychloroquine ；自噬作用

國際替代計量

HYPOTHESIS: DOES ＂AUTOPHAGY PARADOX＂ STRATEGY TO STANDARD THERAPY OF GLIOBLASTOMA MULTIFORME GAIN BENEFIT?

全文下載

主題瀏覽