Advances in Molecular Profiling and Developing Clinical Trials of CNS Germ Cell Tumors: Present and Future Directions

Curr Oncol Rep. 2022 Jan;24(1):105-112. doi: 10.1007/s11912-022-01195-2. Epub 2022 Jan 20.

Abstract

Purpose of review: The last decade has seen significant improvements in the management and understanding of the pathogenesis of CNS germ cell tumors (GCTs) by studies on genomic and epigenomic analyses, and published results of clinical trials. This review highlights the new findings to stay up-to-date on the knowledge and better inform the future directions.

Recent findings: CNS GCTs are characterized by either MAPK or PI3K pathway mutations. Germinoma has a striking global hypo-methylation, analogous to its hypothesized cell-of-origin; primordial germ cell. Micro RNA cluster mir-371-373 and mir-302/367 are characteristic of GCTs, which have potential for liquid biopsy. Clinical trials have revealed whole-ventricular irradiation for germinoma and local radiotherapy for localized non-germinomatous GCTs seem to be sufficient for tumor control. Advancements in basic, translational, and clinical studies are improving our understanding of this rare disease. Further studies are needed, especially in the field of radiomics, liquid biopsy, genomic structural variants, and treatment stratification, to better structure the future management scheme.

Keywords: Clinical trial; Germ cell tumor; Liquid biopsy; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain Neoplasms* / therapy
  • Central Nervous System Neoplasms* / genetics
  • Central Nervous System Neoplasms* / pathology
  • Central Nervous System Neoplasms* / therapy
  • Clinical Trials as Topic
  • Germinoma* / genetics
  • Germinoma* / pathology
  • Germinoma* / therapy
  • Humans
  • Male
  • Neoplasms, Germ Cell and Embryonal* / genetics
  • Neoplasms, Germ Cell and Embryonal* / therapy
  • Phosphatidylinositol 3-Kinases / genetics
  • Testicular Neoplasms* / genetics