Department of Neurosurgery & Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
Cell Transplant. 2022 Jan-Dec;31:9636897221102903. doi: 10.1177/09636897221102903.
Although brain tumors occur less frequently than other forms of cancer, they have one of the bleakest prognoses with low survival rates. The conventional treatment for brain tumors includes surgery, radiotherapy, and chemotherapy. However, resistance to treatment remains a problem with recurrence shortly following. The resistance to treatment may be caused by cancer stem cells (CSCs), a subset of brain tumor cells with the affinity for self-renewal and differentiation into multiple cell lineages. An emerging approach to targeting CSCs in brain tumors is through repurposing the lipid-lowering medication, lovastatin. Lovastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that impacts the mevalonate pathway. The inhibition of intermediates in the mevalonate pathway affects signaling cascades and oncogenes associated with brain tumor stem cells (BTSC). In this review, we show the possible mechanisms where lovastatin can target BTSC for different varieties of malignant brain tumors.
尽管脑肿瘤的发病率低于其他形式的癌症，但由于生存率低，其预后最为恶劣。脑肿瘤的常规治疗包括手术、放疗和化疗。然而，治疗耐药仍然是一个问题，在治疗后不久就会复发。治疗耐药可能是由癌症干细胞（CSC）引起的，CSC 是脑肿瘤细胞的一个亚群，具有自我更新和分化为多个细胞谱系的能力。一种针对脑肿瘤 CSC 的新兴方法是重新利用降脂药物洛伐他汀。洛伐他汀是一种 3-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂，它影响甲羟戊酸途径。甲羟戊酸途径中间产物的抑制会影响与脑肿瘤干细胞（BTSC）相关的信号级联和癌基因。在这篇综述中，我们展示了洛伐他汀可以针对不同类型的恶性脑肿瘤靶向 BTSC 的可能机制。
