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Review
. 2017 Oct 26:6:1892.
doi: 10.12688/f1000research.11493.1. eCollection 2017.

Glioblastoma update: molecular biology, diagnosis, treatment, response assessment, and translational clinical trials

Frank Lieberman  1
Affiliations
Review

Glioblastoma update: molecular biology, diagnosis, treatment, response assessment, and translational clinical trials

Frank Lieberman. F1000Res. .

Abstract

This is an exciting time in neuro-oncology. Discoveries elucidating the molecular mechanisms of oncogenesis and the molecular subtypes of glioblastoma multiforme (GBM) have led to new diagnostic and classification schemes with more prognostic power than histology alone. Molecular profiling has become part of the standard neuropathological evaluation of GBM. Chemoradiation followed by adjuvant temozolomide remains the standard therapy for newly diagnosed GBM, but survival remains unsatisfactory. Patients with recurrent GBM continue to have a dismal prognosis, but neuro-oncology centers with active clinical trial programs are seeing a small but increasing cadre of patients with longer survival. Molecularly targeted therapeutics, personalized therapy based on molecular profiling of individual tumors, and immunotherapeutic strategies are all being evaluated and refined in clinical trials. Understanding of the molecular mechanisms of tumor-mediated immunosuppression, and specifically interactions between tumor cells and immune effector cells in the tumor microenvironment, has led to a new generation of immunotherapies, including vaccine and immunomodulatory strategies as well as T-cell-based treatments. Molecularly targeted therapies, chemoradiation, immunotherapies, and anti-angiogenic therapies have created the need to develop more reliable neuroimaging criteria for differentiating the effects of therapy from tumor progression and changes in blood-brain barrier physiology from treatment response. Translational clinical trials for patients with GBM now incorporate quantitative imaging using both magnetic resonance imaging and positron emission tomography techniques. This update presents a summary of the current standards for therapy for newly diagnosed and recurrent GBM and highlights promising translational research.

Keywords: clinical trials; glioblastoma; immunotherapy; molecular pathology; neuroimaging; pseudoprogression.

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Conflict of interest statement

Competing interests: The author has served on the scientific advisory board for Novocure, has served on scientific advisory panels for Genentech and Roche Pharmaceuticals, and has appeared as a discussant in a paid appearance for Medscape WebMD.No competing interests were disclosed.No competing interests were disclosed.

References

    1. McNeill K, Aldape K, Fine HA: Adult High-Grade (Diffuse) Glioma.In: Karajannis MA, Zagzag D, editors. Molecular Pathology of Nervous System Tumors New York, NY: Springer New York;2015;77–93. 10.1007/978-1-4939-1830-0_6 - DOI
    1. Seystahl K, Wick W, Weller M: Therapeutic options in recurrent glioblastoma--An update. Crit Rev Oncol Hematol. 2016;99:389–408. 10.1016/j.critrevonc.2016.01.018 - DOI - PubMed

    2. F1000 Recommendation

    1. Bell EH, Pugh SL, McElroy JP, et al. : Molecular-Based Recursive Partitioning Analysis Model for Glioblastoma in the Temozolomide Era: A Correlative Analysis Based on NRG Oncology RTOG 0525. JAMA Oncol. 2017;3(6):784–92. 10.1001/jamaoncol.2016.6020 - DOI - PMC - PubMed

    2. F1000 Recommendation

    1. Stupp R, Taillibert S, Kanner AA, et al. : Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015;314(23):2535–43. 10.1001/jama.2015.16669 - DOI - PubMed
    1. Norden AD, Drappatz J, Wen PY: Antiangiogenic therapy in malignant gliomas. Curr Opin Oncol. 2008;20(6):652–61. 10.1097/CCO.0b013e32831186ba - DOI - PubMed