Epigenetic modulators for brain cancer stem cells: Implications for anticancer treatment

doi:10.4252/wjsc.v13.i7.670

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World Journal of Stem Cells

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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
Entinostat	iHDAC (benzamide derivates)	Class I	Brain stem neoplasm	Phase I	Entinostat 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, IV	Recurrent glioma	Phase I	Panobinostat and Stereotactic Radiation Therapy in Treating Patients With Brain Tumors
			High-grade meningioma
			Brain metastasis
Panobinostat (LBH589)	iHDAC (hydroxymic acids)	Class I, II, IV	Diffuse intrinsic pontine glioma	Phase I	Phase 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, IV	Recurrent malignant gliomas	Phase II	Phase II Trial of LBH589 (Panobinostat) in Adult Patients With Recurrent Malignant Gliomas
Valproic Acid	iHDAC (fatty acid derivates)	Class I, II	GBM WHO grade IV	Phase III	International 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 Acid	iHDAC (fatty acid derivates)	Class I, II	Brain metastasis	Phase I	Phase I Study of Temozolomide, Valproic Acid and Radiation Therapy in Patients With Brain Metastases
Valproic Acid	iHDAC (fatty acid derivates)	Class I, II	Neuroectodermal tumor	Phase I	Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases
			Brain metastases
			Advanced cancer
Valproic Acid	iHDAC (fatty acid derivates)	Class I, II	Brain tumors	Phase II	Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors
Valproic Acid	iHDAC (fatty acid derivates)	Class I, II	High grade gliomas	Phase II
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Brain cancer	Phase I/II	Phase I/II Vorinostat, Erlotinib and Temozolomide for Recurrent Glioblastoma Multiforme
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	GBM multiforme	Phase I/II
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Adult giant cell GBM	Phase II	Vorinostat and Bortezomib in Treating Patients With Progressive, Recurrent Glioblastoma Multiforme
			Adult GBM
			Adult gliosarcoma
			Recurrent adult brain tumor
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Adult giant cell GBM	Phase II	Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
			Adult GBM
			Adult gliosarcoma
			Recurrent adult brain tumor
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Recurrent GBM multiforme	Phase II	Ph II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients
			Malignant glioma
			Adult brain tumor
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Brain cancer	Phase I	Phase 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-HDAC	Brain tumor	Phase I/II	Suberoylanilide Hydroxamic Acid (SAHA), Bevacizumab, Daily Temozolomide for Recurrent Malignant Gliomas
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	GBM	Phase I/II
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Brain metastases	Phase I	Study of the Combination of Vorinostat and Radiation Therapy for the Treatment of Patients With Brain Metastases
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Adult GBM	Not applicable	Magnetic 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-HDAC	Adult anaplastic astrocytoma	Phase I	Vorinostat 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-HDAC	Medulloblastoma	Phase I	Vorinostat 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-HDAC	Brain metastasis	Phase II	Vorinostat and Concurrent Whole Brain Radiotherapy for Brain Metastasis
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Adult anaplastic astrocytoma	Phase I	High-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-HDAC	GBM	Phase I	Pembrolizumab and Vorinostat Combined With Temozolomide for Newly Diagnosed Glioblastoma
			Brain tumor
			GBM
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Brain stem glioma	Phase II/III	Vorinostat, 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-HDAC	Adult GBM	Not applicable	Magnetic 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-HDAC	Adult anaplastic astrocytoma	Phase I	Vorinostat 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-HDAC	Medulloblastoma	Phase I	Vorinostat 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-HDAC	Brain metastasis	Phase II	Vorinostat and Concurrent Whole Brain Radiotherapy for Brain Metastasis
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Adult anaplastic astrocytoma	Phase I	High-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-HDAC	GBM	Phase I	Pembrolizumab and Vorinostat Combined With Temozolomide for Newly Diagnosed GBM
			Brain tumor
			GBM
Vorinostat (SAHA)	iHDAC (hydroxymic acids)	Pan-HDAC	Brain stem glioma	Phase II/III	Vorinostat, 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-HDAC	Childhood atypical teratoid/rhabdoid tumor	Phase I	Vorinostat 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

HDAC: Histone deacetylases; iHDAC: HDAC inhibitors; DIPG: Diffuse intrinsic pontine gliomas; WHO: World Health Organization; Ph: Phase; SRS: Stereotactic radiosurgery; GBM: Glioblastoma.

Citation: Abballe L, Miele E. Epigenetic modulators for brain cancer stem cells: Implications for anticancer treatment. World J Stem Cells 2021; 13(7): 670-684
URL: https://www.wjgnet.com/1948-0210/full/v13/i7/670.htm
DOI: https://dx.doi.org/10.4252/wjsc.v13.i7.670