Opinion Review
Copyright ©The Author(s) 2021.
World J Stem Cells. Jul 26, 2021; 13(7): 670-684
Published online Jul 26, 2021. doi: 10.4252/wjsc.v13.i7.670
Table 1 Histone deacetylases inhibitors in clinical trial for brain cancer treatment
Compound
Class
Target
Conditions
Phase of clinical trial
Study title
EntinostatiHDAC (benzamide derivates)Class IBrain stem neoplasmPhase IEntinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors
Pineal region neoplasm
Recurrent lymphoma
Recurrent malignant solid neoplasm
Recurrent primary central nervous system neoplasm
Recurrent visual pathway glioma
Refractory lymphoma
Refractory malignant solid neoplasm
Refractory primary central nervous system neoplasm
Refractory visual pathway glioma
Panobinostat (LBH589)iHDAC (hydroxymic acids)Class I, II, IVRecurrent gliomaPhase IPanobinostat and Stereotactic Radiation Therapy in Treating Patients With Brain Tumors
High-grade meningioma
Brain metastasis
Panobinostat (LBH589)iHDAC (hydroxymic acids)Class I, II, IVDiffuse intrinsic pontine gliomaPhase IPhase I Study of Marizomib + Panobinostat for Children With DIPG
Pediatric brainstem glioma
Pediatric brainstem gliosarcoma recurrent pediatric cancer
Pediatric brain tumor
Diffuse glioma
Panobinostat (LBH589)iHDAC (hydroxymic acids)Class I, II, IVRecurrent malignant gliomasPhase IIPhase II Trial of LBH589 (Panobinostat) in Adult Patients With Recurrent Malignant Gliomas
Valproic AcidiHDAC (fatty acid derivates)Class I, IIGBM WHO grade IVPhase IIIInternational Cooperative Phase III Trial of the HIT-HGG Study Group (HIT-HGG-2013)
Diffuse midline glioma histone 3 K27M WHO grade IV
Anaplastic astrocytoma WHO grade III
Diffuse intrinsic pontine glioma
Gliomatosis cerebri
Valproic AcidiHDAC (fatty acid derivates)Class I, IIBrain metastasisPhase IPhase I Study of Temozolomide, Valproic Acid and Radiation Therapy in Patients With Brain Metastases
Valproic AcidiHDAC (fatty acid derivates)Class I, IINeuroectodermal tumorPhase IValproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases
Brain metastases
Advanced cancer
Valproic AcidiHDAC (fatty acid derivates)Class I, IIBrain tumorsPhase IIValproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors
High grade gliomas
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACBrain cancerPhase I/IIPhase I/II Vorinostat, Erlotinib and Temozolomide for Recurrent Glioblastoma Multiforme
GBM multiforme
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACAdult giant cell GBMPhase IIVorinostat and Bortezomib in Treating Patients With Progressive, Recurrent Glioblastoma Multiforme
Adult GBM
Adult gliosarcoma
Recurrent adult brain tumor
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACAdult giant cell GBMPhase IIVorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
Adult GBM
Adult gliosarcoma
Recurrent adult brain tumor
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACRecurrent GBM multiformePhase IIPh II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients
Malignant glioma
Adult brain tumor
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACBrain cancerPhase IPhase I Vorinostat Concurrent With Stereotactic Radiosurgery (SRS) in Brain Metastases From Non-Small Cell Lung Cancer
Neoplasm metastasis
Lung cancer
Carcinoma, non-small-cell lung
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACBrain tumorPhase I/IISuberoylanilide Hydroxamic Acid (SAHA), Bevacizumab, Daily Temozolomide for Recurrent Malignant Gliomas
GBM
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACBrain metastasesPhase IStudy of the Combination of Vorinostat and Radiation Therapy for the Treatment of Patients With Brain Metastases
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACAdult GBMNot applicableMagnetic Resonance Spectroscopy Imaging in Predicting Response to Vorinostat and Temozolomide in Patients With Recurrent or Progressive Glioblastoma
Depression
Recurrent adult brain tumor
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACAdult anaplastic astrocytomaPhase IVorinostat and Temozolomide in Treating Patients With Malignant Gliomas
Adult anaplastic oligodendrogliomaAdult giant cell GBM
Adult GBM
Adult gliosarcomaAdult mixed glioma
Recurrent adult brain neoplasm
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACMedulloblastomaPhase IVorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System
Pineoblastoma
Supratentorial embryonal tumor
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACBrain metastasisPhase IIVorinostat and Concurrent Whole Brain Radiotherapy for Brain Metastasis
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACAdult anaplastic astrocytomaPhase IHigh-Dose Vorinostat and Fractionated Stereotactic Body Radiation Therapy in Treating Patients With Recurrent Glioma
Adult anaplastic oligodendroglioma
Adult giant cell GBM
Adult GBM
Adult gliosarcoma
Adult mixed glioma
Recurrent adult brain neoplasm
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACGBMPhase IPembrolizumab and Vorinostat Combined With Temozolomide for Newly Diagnosed Glioblastoma
Brain tumor
GBM
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACBrain stem gliomaPhase II/IIIVorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma
Cerebral astrocytoma
Childhood cerebellar anaplastic astrocytoma
Childhood cerebral anaplastic astrocytoma
Childhood spinal cord neoplasm
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACAdult GBMNot applicableMagnetic Resonance Spectroscopy Imaging in Predicting Response to Vorinostat and Temozolomide in Patients With Recurrent or Progressive Glioblastoma
Depression
Recurrent adult brain tumor
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACAdult anaplastic astrocytomaPhase IVorinostat and Temozolomide in Treating Patients With Malignant Gliomas
Adult anaplastic oligodendroglioma
Adult giant cell GBM
Adult GBM
Adult gliosarcoma
Adult mixed glioma
Recurrent adult brain neoplasm
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACMedulloblastomaPhase IVorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System
Pineoblastoma
Supratentorial embryonal tumor
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACBrain metastasisPhase IIVorinostat and Concurrent Whole Brain Radiotherapy for Brain Metastasis
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACAdult anaplastic astrocytomaPhase IHigh-Dose Vorinostat and Fractionated Stereotactic Body Radiation Therapy in Treating Patients With Recurrent Glioma
Adult anaplastic oligodendroglioma
Adult giant cell GBM
Adult GBM
Adult gliosarcoma
Adult mixed glioma
Recurrent adult brain neoplasm
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACGBMPhase IPembrolizumab and Vorinostat Combined With Temozolomide for Newly Diagnosed GBM
Brain tumor
GBM
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACBrain stem gliomaPhase II/IIIVorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma
Cerebral astrocytoma
Childhood cerebellar anaplastic astrocytoma
Childhood cerebral anaplastic astrocytoma
Childhood spinal cord neoplasm
Vorinostat (SAHA)iHDAC (hydroxymic acids)Pan-HDACChildhood atypical teratoid/rhabdoid tumorPhase IVorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors
Childhood central nervous system choriocarcinoma
Childhood central nervous system embryonal tumor and other
Table 2 DNA methyltransferase inhibitors in clinical trial for brain cancer treatment
Compound
Class
Target
Conditions
Phase of clinical trial
Study title
5-Azacytidine DNMTiPan-DNMTBrain tumor recurrentEarly Phase 1Infusion of 5-Azacytidine (5-AZA) Into the Fourth Ventricle in Children With Recurrent Posterior Fossa Ependymoma
AzacitidineDNMTiPan-DNMTGBM multiformeOtherPhase 1Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies
5-AzacytidineDNMTiPan-DNMTRecurrent childhood CNS tumorPhase 1Treatment of Children With Recurrent Refractory Brain/Solid Tumors and Recurrent Ependymoma
Ependymoma, recurrent childhood
Childhood solid tumor