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. Author manuscript; available in PMC: 2019 Mar 1.
Published in final edited form as: J Neurooncol. 2017 Dec 12;137(1):155–169. doi: 10.1007/s11060-017-2708-1

Table 2.

For each of the 17 patients in the Michigan Cohort, a clinical description is provided along with the genomic pathway that was profiled for that specific patient. The potential drug options were listed along with the individual scoring for each drug. The targeted therapy that the CNS TAP tool predicted is juxtaposed next to the actual targeted therapy that was chosen to treat the specific patient.

CNS TAP Tool: University of Michigan Patients
Patient
Number		 Age at
Enrollment
(years)		 Clinical
diagnosis		 Genomic
findings		 Drug Pathway Tumor
line/
pre-
clinical
data
(in
vitro)		 Tumor
line/
pre-
clinical
data
(in
vivo)		 Phase
I
safety
data		 CNS
Data
with
response		 Brain
penetration		 FDA
approval		 Clonality/
variant
allele
fraction
(%)		 Variant
tier
score		 Relevant
clinical
trial		 Total
Points		 Drug
Predicted		 Drug
Chosen
1 1 GBM PDGFRA amplicafication Dasatinib PDGFR 4 6 6 5 10 10 5 3 0 49 Dasatanib Dasatinib
Pazopanib PDGFR 4 6 6 5 5 10 5 3 0 44
Sunitinib PDGFR 2 6 6 5 0 10 5 3 0 37
Ponatinib PDGFR 4 3 0 0 10 10 5 3 0 35
Sorafenib PDGFR 2 0 6 0 0 10 5 3 0 26
Crenolanib PDGFR 2 0 3 0 0 0 5 3 0 13
2 6 GBM H3F3A point mutation Panobinostat HDAC 2 6 6 10 0 10 0 3 0 37 Panobinostat Panobinostat
Vorinostat HDAC 2 6 6 −10 10 10 0 3 0 27
CDK4 amplification Ribociclib CDK 2 0 6 0 10 10 5 3 0 36 Ribociclib Palbociclib
Abemaciclib CDK 2 6 0 10 5 0 5 3 0 31
Palbociclib CDK 2 6 0 0 0 10 5 3 0 26
3 5 DIPG PIK3CA activating mutation Everolimus PI3K/mTOR 2 3 6 10 5 10 0 6 0 42 Everolimus Everolimus
GDC-0084 PI3K/mTOR 4 0 6 10 10 0 0 6 0 36
BKM120 PI3K/mTOR 4 0 0 0 5 0 0 6 0 15
MK-2206 AKT 4 6 6 0 0 0 0 6 0 22
Perifosine AKT 2 0 6 0 0 0 0 6 0 14
HIST1H3B activating mutation Panobinostat HDAC 2 6 6 10 0 10 5 3 0 42 Panobinostat Panobinostat
Vorinostat HDAC 2 6 6 −10 10 10 5 3 0 32
4 1 GBM PDGFB amplification Dasatinib PDGFR 4 6 6 5 10 10 5 3 0 49 Dasatanib Dasatinib
Pazopanib PDGFR 4 6 6 5 5 10 5 3 0 44
Sunitinib PDGFR 2 6 6 5 0 10 5 3 0 37
Ponatinib PDGFR 4 3 0 0 10 10 5 3 0 35
Sorafenib PDGFR 2 0 6 0 0 10 5 3 0 26
Crenolanib PDGFR 2 0 3 0 0 0 5 3 0 13
5 8 Spinal anaplastic OD FGFR activating mutation Ponatinib FGFR 4 6 0 0 10 10 5 6 0 41 Ponatinib Everolimus
Pazopanib FGFR 2 0 6 5 5 10 5 6 0 39
NF1 mutation Trametinib MEK 2 0 3 5 10 10 0 3 0 33
Selumetinib MEK 4 0 0 0 10 10 0 3 0 27
6 13 DIPG FGFR3 activating mutation Ponatinib FGFR 4 6 0 0 10 10 5 6 0 41 Ponatinib Ponatinib
Pazopanib FGFR 2 0 6 5 5 10 5 6 0 39
H3.3 mutation Panobinostat HDAC 2 6 6 10 0 10 0 3 0 37
Vorinostat HDAC 2 6 6 −10 10 10 0 3 0 27
7 15 GBM TSC2 inactivating mutation Everolimus PI3K/mTOR 2 3 6 10 5 10 5 3 0 44 Everolimus Everolimus
GDC-0084 PI3K/mTOR 4 0 6 10 10 0 5 3 0 38
BKM120 PI3K/mTOR 4 0 0 0 5 0 5 3 0 17
8 17 GBM NF1 homozygous loss Trametinib MEK 2 0 3 5 10 10 5 3 0 38 Trametinib Trametinib
Selumetinib MEK 4 0 0 0 10 10 5 3 0 32
H3F3A point mutation Panobinostat HDAC 2 6 6 10 0 10 0 3 0 37 Panobinostat Vorinostat
Vorinostat HDAC 2 6 6 −10 10 10 0 3 0 27
9 17 GBM PDGFRA mutation Dasatinib PDGFR 4 6 6 5 10 10 5 3 0 49 Dasatanib Dasatinib
Pazopanib PDGFR 4 6 6 5 5 10 5 3 0 44
Sunitinib PDGFR 2 6 6 5 0 10 5 3 0 37
Ponatinib PDGFR 4 3 0 0 10 10 5 3 0 35
Sorafenib PDGFR 2 0 6 0 0 10 5 3 0 26
Crenolanib PDGFR 2 0 3 0 0 0 5 3 0 13
10 11 Anaplastic OD FGFR3-PHGDH fusion Ponatinib FGFR 4 6 0 0 10 10 5 6 0 41 Ponatinib Ponatinib
Pazopanib FGFR 2 0 6 5 5 10 5 6 0 39
11 11 Choroid plexus carcinoma NF1 frameshift insertion Trametinib MEK 2 0 3 5 10 10 5 3 0 38 Trametinib Trametinib
Selumetinib MEK 4 0 0 0 10 10 5 3 0 32
12 8 DIPG PIK3CA activating mutation Everolimus PI3K 2 3 6 10 5 10 0 6 0 42 Panobinostat Panobinostat
GDC-0084 PI3K 4 0 6 10 10 0 0 6 0 36
BKM120 PI3K 4 0 0 0 5 0 0 6 0 15
MK-2206 AKT 4 6 6 0 0 0 0 0 0 16
Perifosine AKT 2 0 6 0 0 0 0 0 0 8
H3F3A activating mutation Panobinostat HDAC 2 6 6 10 0 10 5 3 0 42 Everolimus Everolimus
Vorinostat HDAC 2 6 6 −10 10 10 5 3 0 32
13 29 Anaplastic astroblastoma SMARCB1homozygous deletion Alisertib INI1 4 6 6 10 10 0 5 3 0 44 Alisertib Alisertib
Tamoxifen INI1 2 0 0 0 10 10 5 3 0 30
Tazemetostat INI1 2 0 3 0 0 0 5 3 0 13
14 11 GBM EGFR in-frame deletion Osimertinib EGFR 2 6 0 5 10 10 5 3 0 41 Osimertinib Osimertinib
Pazopanib EGFR 2 0 6 5 5 10 5 3 0 36
Erlotinib EGFR 4 0 6 −10 10 10 5 3 0 28
15 3 DIPG PTPN11 mutation Trametinib MEK 2 0 3 5 10 10 5 6 0 41 Trametinib Trametinib
Selumetinib MEK 4 0 0 0 10 10 5 6 0 35
H3.1 mutation Panobinostat HDAC 2 6 6 10 0 10 0 3 0 37
Vorinostat HDAC 2 6 6 −10 10 10 0 3 0 27
16 4 DIPG H3.1 and ACVR1 mutation Panobinostat HDAC 2 6 6 10 0 10 5 3 0 42 Panobinostat Panobinostat
Vorinostat HDAC 2 6 6 −10 10 10 5 3 0 32
17 15 Malignant glioneuronal tumor ROS1-GOPC fusion Entrectinib ALK 4 0 3 10 10 0 5 3 20 55 Entrectinib Entrectinib
Ceritinib ALK 2 0 6 0 10 10 5 3 0 36
Alectanib ALK 2 0 3 0 10 10 5 3 0 33

Abbreviations: GBM = glioblastoma multiforme, PDGFRA = platelet-derived growth factor receptor, HDAC = histone deacetylase, CDK = cyclin-dependent kinase, DIPG = diffuse intrinsic pontine glioma, PI3K = phosphatidylinositol 3-kinase, mTOR = mechanistic target of rapamycin, AKT = protein kinase B, FGFR = fibroblast growth factor receptor, NF = neurofibromatosis, OD = oligodendroglioma, MEK = mitogen-activated protein kinase kinase, TSC = tuberous sclerosis complex, PHGDH = phosphoglycerate dehydrogenase, SMARCB = SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B, INI = integrase interactor, EGFR = epidermal growth factor receptor, PTPN = protein-tyrosine phosphate nonreceptor, ROS1-GOPC = Golgi-associated PDZ and coiled-coil domains-containing gene, ALK = anaplastic lymphoma kinase.