Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School, Spaulding Rehabilitation Hospital and Brigham and Women's Hospital, Division of Spinal Cord Injury Research, VA Boston Healthcare System, Boston, MA, USA.
Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School, Spaulding Rehabilitation Hospital and Brigham and Women's Hospital, Division of Spinal Cord Injury Research, VA Boston Healthcare System, Boston, MA, USA; Current affiliation: Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA.
Exp Neurol. 2019 Jan;311:135-147. doi: 10.1016/j.expneurol.2018.09.010. Epub 2018 Sep 21.
Spinal cord astrocytomas (SCAs) have discernibly unique signatures in regards to epidemiology, clinical oncological features, genetic markers, pathophysiology, and research and therapeutic challenges. Overall, there are presently very limited clinical management options for high grade SCAs despite progresses made in validating key molecular markers and standardizing tumor classification. The endeavors were aimed to improve diagnosis, therapy design and prognosis assessment, as well as to define more effective oncolytic targets. Efficacious treatment for high grade SCAs still remains an unmet medical demand. This review is therefore focused on research state updates that have been made upon analyzing clinical characteristics, diagnostic classification, genetic and molecular features, tumor initiation cell biology, and current management options for SCAs. Particular emphasis was given to basic and translational research endeavors targeting SCAs, including establishment of experimental models, exploration of unique profiles of SCA stem cell-like tumor survival cells, characterization of special requirements for effective therapeutic delivery into the spinal cord, and development of donor stem cell-based gene-directed enzyme prodrug therapy. We concluded that precise understanding of molecular oncology, tumor survival mechanisms (e.g., drug resistance, metastasis, and cancer stem cells/tumor survival cells), and principles of Recovery Neurobiology can help to create clinically meaningful experimental models of SCAs. Establishment of such systems will expedite the discovery of efficacious therapies that not only kill tumor cells but simultaneously preserve and improve residual neural function.
脊髓星形细胞瘤（SCA）在流行病学、临床肿瘤学特征、遗传标志物、病理生理学以及研究和治疗挑战方面具有明显独特的特征。尽管在验证关键分子标志物和标准化肿瘤分类方面取得了进展，但目前对于高级别 SCA 来说，临床管理选择非常有限。这些努力旨在改善诊断、治疗设计和预后评估，并确定更有效的溶瘤靶点。有效的高级别 SCA 治疗仍然是未满足的医疗需求。因此，本综述重点介绍了在分析临床特征、诊断分类、遗传和分子特征、肿瘤起始细胞生物学以及 SCA 的当前治疗选择方面所取得的研究进展。特别强调了针对 SCA 的基础和转化研究努力，包括建立实验模型、探索 SCA 干细胞样肿瘤存活细胞的独特特征、描述有效递送到脊髓的特殊要求以及开发基于供体干细胞的基因定向酶前药治疗。我们得出结论，精确理解分子肿瘤学、肿瘤存活机制（例如，耐药性、转移和癌症干细胞/肿瘤存活细胞）以及恢复神经生物学原则有助于创建具有临床意义的 SCA 实验模型。建立这样的系统将加速发现有效的治疗方法，这些方法不仅能杀死肿瘤细胞，而且还能同时保护和改善残留的神经功能。
