Heimberger Amy B
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Unit 442, 1515 Holcombe Boulevard, Houston TX 77030-4009, USA.
Surg Neurol Int. 2011;2:163. doi: 10.4103/2152-7806.89886. Epub 2011 Nov 14.
High-grade primary and metastatic central nervous system (CNS) tumors are common, deadly, and refractory to conventional therapy and continue to be therapeutically challenging. A key nodal transcriptional factor, the signal transducer and activator of transcription 3 (STAT3), drives the fundamental components of tumor malignancy and metastases in the CNS by enhancing proliferation, angiogenesis, invasion, metastasis, and immunosuppression. The introduction of STAT3 inhibitors in clinical trials for this patient population is imminent.
STAT3 inhibitors have been extensively tested in a variety of preclinical murine models.
The STAT3 inhibitor, WP1066, has displayed marked efficacy with minimal toxicity against malignancy in murine models, including established intracerebral tumors. The mechanism of this in vivo efficacy of the STAT3 blockade agents is a combination of direct tumor cytotoxicity and immune cytotoxic clearance.
Given their direct antitumor cytotoxic effects, STAT3 inhibitors may exert therapeutic activity in the monotherapy setting but may also have compelling use as immunotherapeutic modulators or as a salvage therapy.
高级别原发性和转移性中枢神经系统（CNS）肿瘤常见且致命，对传统治疗具有抗性，在治疗上仍然具有挑战性。关键节点转录因子信号转导子和转录激活子3（STAT3）通过增强增殖、血管生成、侵袭、转移和免疫抑制，驱动CNS肿瘤恶性和转移的基本过程。STAT3抑制剂即将引入针对该患者群体的临床试验。
STAT3抑制剂已在多种临床前小鼠模型中进行了广泛测试。
STAT3抑制剂WP1066在小鼠模型中，包括已形成的脑内肿瘤，显示出显著疗效且对恶性肿瘤毒性极小。STAT3阻断剂这种体内疗效的机制是直接肿瘤细胞毒性和免疫细胞毒性清除的结合。
鉴于其直接的抗肿瘤细胞毒性作用，STAT3抑制剂可能在单药治疗中发挥治疗活性，但也可能作为免疫治疗调节剂或挽救疗法具有引人注目的用途。
