Spinal cord astrocytomas: progresses in experimental and clinical investigations for developing recovery neurobiology-based novel therapies

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.

Keywords: Cancer stem cell; Gene-directed enzyme prodrug therapy; Glioblastoma; Glioma; Intramedullary spinal cord tumor; Recovery neurobiology; Spinal cord astrocytoma; Tumor survival cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Astrocytoma / genetics
  • Astrocytoma / metabolism
  • Astrocytoma / therapy*
  • Genetic Therapy / methods
  • Genetic Therapy / trends*
  • Humans
  • Neurobiology
  • Neurosurgical Procedures / methods
  • Neurosurgical Procedures / trends*
  • Recovery of Function / physiology*
  • Spinal Cord Neoplasms / genetics
  • Spinal Cord Neoplasms / metabolism
  • Spinal Cord Neoplasms / therapy*
  • Stem Cell Transplantation / methods
  • Stem Cell Transplantation / trends*
  • Treatment Outcome