A comprehensive overview on the molecular biology of human glioma: what the clinician needs to know
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REVIEW ARTICLE
A comprehensive overview on the molecular biology of human glioma: what the clinician needs to know P. D. Delgado‑López1 · P. Saiz‑López2 · R. Gargini3,4 · E. Sola‑Vendrell5 · S. Tejada6 Received: 22 January 2020 / Accepted: 16 March 2020 © Federación de Sociedades Españolas de Oncología (FESEO) 2020
Abstract The molecular biology of human glioma is a complex and fast-growing field in which basic research needs to meet clinical expectations in terms of anti-tumor efficacy. Although much effort is being done in molecular biology research, significant contribution to the quality of life and overall survival still lacks. The vastness of molecular biology literature makes it virtually impossible for clinicians to keep up to date in the field. This paper reviews some practical concepts regarding glioma tumorigenesis from the clinician’s perspective. Five main aspects are discussed: major intracellular signaling pathways involved in glioma formation; genomic, epigenetic and transcriptomic relevant features of glioma; the prognostic and predictive values of molecular markers according to the new WHO classification of glial tumors; the importance of molecular and cellular heterogeneity in glioblastoma, responsible for its therapy resistance; and the interaction between glioma and the immune system, in view of the novel and promising targeted therapies. Keywords Glioma · Glioblastoma · Malignant glioma · Molecular biology · Epigenetics · Transcriptomics
Introduction Human glioma comprises a group of heterogeneous primary brain neoplasms that, from a basic histopathologic perspective, can be readily classified in two domains. First, lowgrade glioma (LGG), which seems to benefit from maximal safe resection, eventual reoperation and adjuvant radiation and/or chemotherapy [1], and second, high-grade glioma (HGG), which also benefits from maximal resection and mandatory postoperative chemoradiation [2]. However, * P. D. Delgado‑López [email protected] 1
Servicio de Neurocirugía, Hospital Universitario de Burgos, Avda Islas Baleares 3, 09006 Burgos, Spain
2
Servicio Anatomía Patológica, Hospital Universitario de Burgos, Burgos, Spain
3
Unidad de Neurooncología, Instituto de Salud Carlos III-UFIEC, Madrid, Spain
4
Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Madrid, Spain
5
Servicio de Anatomía Patológica, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
6
Servicio de Neurocirugía, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
whereas therapy for LGG is currently able to extend life expectancy over 10–15 years on average from diagnosis [3], aggressive treatment against glioblastoma (GBM) yields a modest 14-month overall survival [4]. Reasons for this poor prognosis include the infiltrative nature of malignant glioma, which precludes disease cure even in the event of supramaximal resection, and its inherent resistance to radiation and chemotherapy [5]. This resistance seems to be linked to intricate biochemical and signaling pathways alteration
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