Subtype and pathway specific responses to anti-cancer ... · 4 compared to luminal and ERBB2AMP...
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1 Subtype and pathway specific responses to anti-cancer compounds in breast cancer Heiser, et al. Supplementary Information Association of growth rate and response to therapeutic agents In general, we found that luminal subtype cell lines grew more slowly than basal or claudin-low cells (Kruskal-Wallis test p = 0.006, Fig. S3A and Table S1) and the range of doubling times was broad (18 to 300 hours). This raised the possibility that the most sensitive cell lines were those that grew most rapidly. We tested this hypothesis by assessing the effects of subtype and doubling time simultaneously with an ANCOVA (see details below) and found that 20 of 23 subtype-specific compounds had better associations with subtype than with doubling time (mean log ratio of p-values = 0.87, standard deviation 1.09). Moreover, 11 of 23 subtype-specific compounds were most effective in the most slowly growing luminal cell lines (Table 1). One agent, 5- fluorouracil, was not significant in the subtype test alone but showed strong significance in the ANCOVA model for both class and doubling time. (Fig. S3B). We conclude that in most cases, the 3-day proliferation assay detects molecular signature-specific responses that are not strongly influenced by growth rate. To assess the effects of cell line subtype and growth rate on drug sensitivity, we performed a set of 2-way analysis of covariance (ANCOVA) tests, one for each of the three cell line classification schemes: i) luminal vs. basal vs. claudin-low; ii) luminal vs. basal + claudin-low; and iii) ERBB2 AMP vs. non-ERBB2 AMP . This yielded 6 sets of p- values (2 main effects x 3 classification schemes); we separately adjusted the two sets of main effect p-values for multiple comparisons. We used the R functions lm and Anova (available as part of the car package). Integrated Pathway Analysis Integration of copy number, gene expression and pathway interaction data was performed using the PARADIGM software(1). Briefly, this procedure infers integrated pathway levels (IPLs) for genes, complexes, and processes using pathway interactions and genomic and functional genomic data from a single cell line or patient sample. TCGA breast cancer data was obtained from the TCGA DCC on November 7, 2010. TCGA and cell line gene expression data were median probe centered within each data set separately. All of the values in each of these datasets (either the cell lines or TCGA tumor samples) were rank transformed and converted to –log10 rank ratios before supplying to PARADIGM. Pathways were obtained in BioPax Level 2 format on October 13, 2010 from http://pid.nci.nih.gov/ and included NCI-PID, Reactome, and BioCarta databases. Interactions were combined into a merged Superimposed Pathway (SuperPathway). Genes, complexes, and abstract processes (e.g. “cell cycle”) were retained as pathway concepts. Before merging gene concepts, all gene identifiers were translated into HUGO nomenclature. All interactions were included and no attempt was made to resolve conflicting influences. A breadth-first undirected traversal starting from P53 (the most
Transcript of Subtype and pathway specific responses to anti-cancer ... · 4 compared to luminal and ERBB2AMP...
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Subtype and pathway specific responses to anti-cancer compounds in breast cancer Heiser, et al. Supplementary Information Association of growth rate and response to therapeutic agents In general, we found that luminal subtype cell lines grew more slowly than basal or claudin-low cells (Kruskal-Wallis test p = 0.006, Fig. S3A and Table S1) and the range of doubling times was broad (18 to 300 hours). This raised the possibility that the most sensitive cell lines were those that grew most rapidly. We tested this hypothesis by assessing the effects of subtype and doubling time simultaneously with an ANCOVA (see details below) and found that 20 of 23 subtype-specific compounds had better associations with subtype than with doubling time (mean log ratio of p-values = 0.87, standard deviation 1.09). Moreover, 11 of 23 subtype-specific compounds were most effective in the most slowly growing luminal cell lines (Table 1). One agent, 5-fluorouracil, was not significant in the subtype test alone but showed strong significance in the ANCOVA model for both class and doubling time. (Fig. S3B). We conclude that in most cases, the 3-day proliferation assay detects molecular signature-specific responses that are not strongly influenced by growth rate. To assess the effects of cell line subtype and growth rate on drug sensitivity, we performed a set of 2-way analysis of covariance (ANCOVA) tests, one for each of the three cell line classification schemes: i) luminal vs. basal vs. claudin-low; ii) luminal vs. basal + claudin-low; and iii) ERBB2AMP vs. non-ERBB2AMP. This yielded 6 sets of p-values (2 main effects x 3 classification schemes); we separately adjusted the two sets of main effect p-values for multiple comparisons. We used the R functions lm and Anova (available as part of the car package). Integrated Pathway Analysis Integration of copy number, gene expression and pathway interaction data was performed using the PARADIGM software(1). Briefly, this procedure infers integrated pathway levels (IPLs) for genes, complexes, and processes using pathway interactions and genomic and functional genomic data from a single cell line or patient sample. TCGA breast cancer data was obtained from the TCGA DCC on November 7, 2010. TCGA and cell line gene expression data were median probe centered within each data set separately. All of the values in each of these datasets (either the cell lines or TCGA tumor samples) were rank transformed and converted to –log10 rank ratios before supplying to PARADIGM. Pathways were obtained in BioPax Level 2 format on October 13, 2010 from http://pid.nci.nih.gov/ and included NCI-PID, Reactome, and BioCarta databases. Interactions were combined into a merged Superimposed Pathway (SuperPathway). Genes, complexes, and abstract processes (e.g. “cell cycle”) were retained as pathway concepts. Before merging gene concepts, all gene identifiers were translated into HUGO nomenclature. All interactions were included and no attempt was made to resolve conflicting influences. A breadth-first undirected traversal starting from P53 (the most
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connected component) was performed to build one single component. The resulting merged pathway structure contained a total of 8768 concepts representing 3491 proteins, 4757 complexes, and 520 processes. Expectation-Maximization parameters for PARADIGM were trained on the cell line data and then applied to the TCGA samples. Data from the cell lines and tumor samples were then combined into a single data matrix. Any entry without at least 1 value above 0.5 IPL in either the data from cell lines or tumor samples was removed from further analysis. TCGA and cell line clustering Using PARADIGM IPLs, cell lines were clustered together with TCGA tumor samples to determine if cell lines were similar to tumor samples of the same subtype. Well-studied areas of the SuperPathway contain genes with many interactions (hubs) and large signaling chains of many intermediate complexes and abstract processes for which no direct data is available. To avoid bias toward due to the presence of hubs, pathway concepts with highly correlated vectors (Pearson correlation coefficient > 0.9) across both the cell line and tumor samples were unified into a single vector prior to clustering. This unification resulted in 2351 non-redundant vectors from the original 8768 pathway concepts. Samples were clustered using the resulting set of non-redundant concepts. The matrix of inferred pathway activities for the 46 breast cancer cell lines and 183 TCGA tumor samples was clustered using complete linkage hierarchical agglomerative clustering implemented in the Eisen Cluster software package version 3.0(2). Uncentered Pearson correlation was used as the metric for the pathway concepts and Euclidean distance was used for sample metric (Fig. S4). To quantify the degree to which cell lines clustered with tumor samples of the same subtype, we compared two distributions of t-statistics derived from Pearson correlations (Fig. S5). Let Cs be the set of cell lines of subtype s. Similarly, let Ts be the set of TCGA tumor samples of subtype s. For example, Cbasal and Tbasal are the set of all basal cell lines and basal tumor samples respectively. The first distribution was made up of t-statistics derived from the Pearson correlations between every possible pair containing a cell line and tumor sample of the same subtype; i.e. for all subtypes s, every pairwise correlation t-statistic was computed between a pair (c, t) such that c ∈ Cs and t ∈ Ts. The second distribution was made of correlation t-statistics between cell lines of different subtypes; i.e. computed over pairs (c, c’) such that c ∈ Cs and c’ ∈ Cs’ and s ≠ s’. We performed a Kolmogorov-Smirnov test to compare the distributions. We repeated this analysis using samples from the same source (cell line or tumor) to verify that cells of the same subtype have overall pathway activities that are more similar than cells of different subtypes. As above, the first distribution was made up of t-statistics between pairs of samples of the same subtype and the same origin (cell line or tumor). The second distribution was made of correlation t-statistics between samples of different subtypes again from the same origin. We assessed the significance of the subpathways by comparing to subnetworks generated from a background model. Specifically, we measured how likely it would be to find the
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identified subnetworks with the observed sizes by chance. To this end, we constructed a background set of subnetworks computed from 1000 simulations in which samples were randomly partitioned into two equal bins, which simulated groupings of cancer cell lines reflecting no biological relevance. Statistical Analysis of Microarrays (SAM) then was used to compute differential pathway activity scores for each concept and each random partitioning using the same thresholds as with the original subtype definitions. Histograms of the subpathway sizes obtained from the random partitions were compared against the subpathway sizes derived from the original subtypes to gauge significance. Our analysis shows that subnetworks derived from the original basal, luminal, claudin-low, and ERBB2 AMP definitions are significantly larger than those subnetworks obtained from random partitionings. This is true for both the size of the entire subpathway (total number of nodes in the graph) as well as for the largest connected component. Histograms and empirical Z-scores were collected from this random partitioning analysis (see Fig. S6). Supplementary Figure and Table Legends Figure S1. Genomic and transcriptional profiles of the breast cancer cell lines. A. Hierarchical consensus clustering matrix for 55 breast cancer cell lines showing 3 clusters (claudin-low, luminal, basal) based on gene expression signatures. For each cell line combination, color intensity is proportional to consensus. B. DNA copy number aberrations for 43 breast cancer cell lines are plotted with log10(FDR) of GISTIC analysis on the y-axis and chromosome position on the x-axis. Copy number gains are shown in red with positive log10(FDR) and losses are shown in green with negative log10(FDR). Figure S2. GI50 calculations are highly reproducible. A. Each bar represents a count of the frequency of replicated drug/cell line combinations. Most cell lines were tested only one time against a particular compound, but some drug/cell line combinations were tested multiple times. B. Each boxplot represents the distribution of median absolute deviations for drug/cell line pairs with 3 or 4 replicates. C. Example drug response curves for HCC1395 treated with cisplatin. Data from three experiments are shown, each plotted in a unique color. Each dot represents the growth inhibition following three days of treatment with one of 10 concentrations of cisplatin. For each dose of each experiment, measurements are performed in triplicate. The x-axis represents increasing cisplatin concentration; the y-axis indicates growth inhibition following treatment. A single curve is fit to the set of 30 data points (3 untreated and 27 treated). The vertical line represents GI50, which is extrapolated from the fitted curve. Across multiple experimental replicates, the dose-response curve is highly reproducible. D, E, F. Example drug response curves for three other cell lines, each treated with a different compound. Convention as in C. Figure S3. Doubling time varies across cell line subtype. A. Growth rate, computed as the median doubling time in hours, of the breast cancer cell lines subtypes are shown as box-plots. The basal and claudin-low subtypes have shorter median doubling time as
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compared to luminal and ERBB2AMP subtypes, Kruskal-Wallis p value (p = 0.006). B. The ANCOVA model shows strong effects of both subtype and growth rate on response to 5-FU. Luminal (black) and basal/claudin-low (red) breast cancer lines each show significant associations to growth rate but have distinct slopes. Figure S4. Heatmap of non-redundant PARADIGM activities for both cell line and TCGA samples. Cluster dendrogram represents Euclidian distance between samples and was created using Eisen Cluster and drawn using Java Treeview. Each row represents a network feature, each column represents a sample (tumor or cell line). Colored bars below dendrogram indicate sample subtype (upper) and sample cohort (lower). Overall, cell lines and tumors are intermixed, and subtypes tend to cluster together, indicating that the tumors and cell lines share many of the same network features. Figure S5. Inferred pathway activities are more strongly correlated within subtypes than within cohorts. A. Histogram of t-statistics derived from Pearson correlations computed between cell lines and TCGA samples of the same subtype (red) compared to t-statistics of Pearson correlations between cell lines of different subtypes (black). X-axis corresponds to the Pearson correlation t-statistic; y-axis shows the density of (cell-line, cell-line) or (cell-line, TCGA sample) pairs. K-S test (p < 1x10-22) indicates cell lines and TCGA samples of the same subtype are more alike than cell lines of other subtypes. B. Pairwise Pearson correlations of cell line samples within the same subgroup (red) versus cell line samples in different subgroups (black). C. Pairwise correlations of TCGA breast cancer samples within the same subgroup (red) versus cell line samples in different subgroups (black). Figure S6. The cell line networks are highly significant. The significance of the subpathways identified by our method was assessed by comparing the size of our subpathways to the size of the subpathways generated from a background model in which cells were randomly partitioned into groups, rather than in the original subtype definitions. The subpathway sizes were measured in two ways, the total number of nodes in the subpathway (A,C,E,G) and the number of nodes in the largest connected component of the subpathway (B,D,F,H). The luminal (A,B), ERBB2 AMP (C,D), claudin-low (E,F), and basal (G,H) subpathway sizes are shown as red dotted lines compared against the distribution of null subpathway sizes. In all cases the subpathway sizes for the true subtype partitioning are significantly larger than the subpathway sizes for the background model. Dataset S1. Transcriptional, genomic and phenotypic characteristics of cell lines in the panel. Dataset S2. Drug response data for each cell line tested against 77 therapeutic compounds. Data are -log10 transformed. These data were used to determine subtype specific responses. Dataset S3. Pearson correlations between drug responses for all compound pairs.
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Dataset S4. Subtype associations for all therapeutic compounds. Both raw p-values and FDR-corrected q-values are shown. Dataset S5. Censored drug response data. GI50 values that are same as maximum experimental concentration used for different drugs were removed. Data are -log10 transformed. These data were used to identify responses associated with copy number aberrations. Dataset S6. Non-redundant PARADIGM activities for cell lines and TCGA samples share similar subtype enrichment. Non-redundant pathway entities are along the rows, with subtype-specific SAM scores along the columns, for cell lines alone, TCGA samples alone, and the combined cell line and tumor samples (“BOTH”) as shown in Figure S4. Each SAM score has been ranked within the source-specific subtype and average ranks were computed between the cell lines and TCGA samples for the same subtype (luminal, basal, claudin-low and ERBB2AMP). Dataset S7. Subtypes for TCGA breast tumor samples, as determined by the TCGA AWG using heirarchical clustering of an intrinsic gene list. Data were obtained from the TCGA on November 6, 2010. Waterfall plots Waterfall plots of breast cancer subtypes and anti-cancer compounds follow after the supplementary figures. Association of clinical subtypes of breast cancer cell lines with 74 anti-cancer compounds. Each bar represents response sensitivity for one cell line, cell lines are ordered by sensitivity (–log10(GI50)) and colored to indicate subtype. PARADIGM Network files Cytoscape files for the PARADIGM breast cancer cell line networks are available at: http://users.soe.ucsc.edu/~jstuart/heiser2011/
References
1. Vaske CJ, et al. (Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM. Bioinformatics 26(12):i237-245.
2. de Hoon MJ, Imoto S, Nolan J, & Miyano S (2004) Open source clustering software. Bioinformatics 20(9):1453-1454.
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AM
B17
5VII
LY2
HC
C31
53
HC
C21
85
SU
M52
PE
SK
BR
3
MD
AM
B13
4VI
CA
MA
1
HC
C19
37
MD
AM
B46
8
AS−252424 (PI3K gamma)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0 Basal
ERBB2AMPLuminalClaudin−low
SU
M14
9PT
MD
AM
B13
4VI
HC
C19
54
MD
AM
B17
5VII
ZR
751
SU
M13
15M
O2
SU
M52
PE
HC
C14
19
HC
C13
95
SU
M18
5PE
MD
AM
B43
6
BT
474
HC
C21
85
CA
MA
1
HC
C19
37
MD
AM
B46
8
HC
C38
MD
AM
B23
1
MD
AM
B36
1
MD
AM
B45
3
MC
F7
BT
483
SK
BR
3
HC
C18
06
ZR
75B
HC
C14
28
T47
D
BT
20
MD
AM
B41
5
AZD6244 (MEK)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5 Basal
LuminalERBB2AMPClaudin−low
SU
M15
9PT
HC
C19
54
MD
AM
B45
3
ZR
75B
HC
C70
SU
M13
15M
O2
AU
565
HC
C21
85
MD
AM
B41
5
SU
M14
9PT
T47
D
BT
474
HC
C38
SK
BR
3
MC
F7
HC
C31
53
MD
AM
B36
1
MD
AM
B13
4VI
MD
AM
B17
5VII
BT
20
BT
483
SU
M18
5PE
ZR
751
UA
CC
812
CA
MA
1
SU
M52
PE
HC
C14
28
HC
C11
87
MD
AM
B46
8
BEZ235 (PI3K)
−lo
g10
GI5
0 (M
)
45
67
8
Claudin−lowERBB2AMPLuminalBasal
UA
CC
812
HC
C14
19
MD
AM
B17
5VII
BT
474
SU
M22
5CW
N
SK
BR
3
SU
M14
9PT
MD
AM
B45
3
HC
C19
54
SU
M13
15M
O2
HC
C70
HC
C18
06
MD
AM
B46
8
HC
C11
43
HC
C21
85
BT
483
HC
C14
28
HC
C38
HC
C19
37
CA
MA
1
ZR
751
SU
M15
9PT
BT
20
ZR
75B
SU
M52
PE
MD
AM
B13
4VI
MD
AM
B43
6
SU
M18
5PE
BIBW 2992 (EGFR and HER2 inhibitor)
−lo
g10
GI5
0 (M
)
56
78
9 ERBB2AMPLuminalBasalClaudin−low
UA
CC
893
HC
C70
HC
C11
87H
CC
1419
HC
C21
85M
DA
MB
175V
IIS
UM
52P
EA
U56
5S
UM
185P
EB
T54
9M
DA
MB
157
MD
AM
B45
3H
CC
1395
HC
C20
2B
T47
4S
UM
149P
TS
UM
159P
TH
CC
1937
SK
BR
3T
47D
MD
AM
B13
4VI
HC
C11
43M
DA
MB
436
HC
C19
54H
CC
3153
SU
M22
5CW
NH
CC
38S
UM
1315
MO
2M
DA
MB
468
CA
MA
1Z
R75
1M
CF
7B
T48
3H
CC
1806
UA
CC
812
MD
AM
B23
1M
DA
MB
415
BT
20H
CC
1428
ZR
75B
600M
PE
LY2
MD
AM
B36
1
Bortezomib (Proteasome, NFkB)
−lo
g10
GI5
0 (M
)
56
78
9
LuminalBasalERBB2AMPClaudin−low
BT
474
SU
M14
9PT
HC
C14
19S
UM
1315
MO
2H
CC
38H
CC
70M
DA
MB
175V
IIH
CC
1954
BT
20S
UM
159P
TH
CC
1937
SU
M52
PE
MD
AM
B36
1H
CC
1806
AU
565
MD
AM
B45
3LY
2M
CF
7M
DA
MB
468
UA
CC
812
HC
C11
87C
AM
A1
BT
483
HC
C31
53H
CC
1428
SK
BR
3H
CC
1143
MD
AM
B43
6H
CC
2185
T47
DZ
R75
B60
0MP
EZ
R75
1M
DA
MB
134V
I
Bosutinib (Src )
−lo
g10
GI5
0 (M
)
3.5
4.0
4.5
5.0
5.5
6.0
6.5 ERBB2AMP
BasalClaudin−lowLuminal
BT
483
HC
C13
95A
U56
5S
UM
149P
TS
KB
R3
HC
C70
UA
CC
812
HC
C18
06H
CC
38S
UM
52P
EH
CC
2185
HC
C11
87B
T54
9S
UM
1315
MO
2Z
R75
30S
UM
159P
TH
CC
3153
HC
C19
37M
DA
MB
175V
IIH
CC
202
LY2
HC
C19
54M
DA
MB
361
MD
AM
B46
8M
DA
MB
453
MD
AM
B43
6H
CC
1419
MD
AM
B23
1M
DA
MB
157
ZR
751
BT
474
T47
DS
UM
185P
EH
CC
1428
HC
C11
4360
0MP
EM
CF
7M
DA
MB
415
MD
AM
B13
4VI
CA
MA
1Z
R75
BU
AC
C89
3
Carboplatin (DNA cross−linker)
−lo
g10
GI5
0 (M
)
3.0
3.5
4.0
4.5
5.0
5.5
6.0 Luminal
Claudin−lowERBB2AMPBasal
HC
C19
54M
DA
MB
468
HC
C70
SU
M52
PE
HC
C31
53H
CC
1937
T47
DH
CC
38H
CC
1419
HC
C20
2S
UM
149P
TB
T54
9H
CC
1806
MD
AM
B41
5M
CF
7H
CC
1395
SU
M15
9PT
HC
C11
43H
CC
1428
BT
474
AU
565
UA
CC
812
MD
AM
B43
6H
CC
2185
600M
PE
SU
M18
5PE
MD
AM
B45
3Z
R75
1Z
R75
BB
T48
3M
DA
MB
175V
IIS
UM
1315
MO
2M
DA
MB
361
MD
AM
B15
7M
DA
MB
134V
IC
AM
A1
LY2
HC
C11
87U
AC
C89
3M
DA
MB
231
SK
BR
3Z
R75
30
CGC−11047 (polyamine analogue)
−lo
g10
GI5
0 (M
)
23
45
6
ERBB2AMPBasalLuminalClaudin−low
T47
DM
DA
MB
157
HC
C11
43H
CC
38S
UM
52P
EU
AC
C81
2M
DA
MB
415
HC
C19
37M
DA
MB
175V
IIH
CC
3153
HC
C18
06S
UM
185P
EB
T54
9U
AC
C89
3H
CC
2185
SU
M15
9PT
HC
C19
54H
CC
70S
UM
149P
TB
T20
600M
PE
ZR
751
CA
MA
1M
DA
MB
134V
IH
CC
1428
MC
F7
AU
565
HC
C14
19M
DA
MB
453
HC
C20
2B
T48
3H
CC
1395
MD
AM
B46
8M
DA
MB
436
BT
474
HC
C11
87M
DA
MB
361
SU
M13
15M
O2
SU
M22
5CW
NS
KB
R3
LY2
MD
AM
B23
1
CGC−11144 (polyamine analogue)
−lo
g10
GI5
0 (M
)
4.5
5.0
5.5
6.0
6.5
7.0
7.5
LuminalClaudin−lowBasalERBB2AMP
HC
C13
95H
CC
70S
UM
149P
TH
CC
38H
CC
202
SU
M52
PE
AU
565
SU
M13
15M
O2
HC
C18
06H
CC
2185
ZR
7530
HC
C11
87H
CC
1937
UA
CC
812
BT
549
SU
M15
9PT
MD
AM
B17
5VII
HC
C19
54T
47D
MD
AM
B46
8M
DA
MB
453
HC
C31
53H
CC
1419
HC
C11
43M
DA
MB
361
LY2
MD
AM
B43
6Z
R75
1M
CF
7M
DA
MB
231
MD
AM
B15
7B
T47
4H
CC
1428
CA
MA
160
0MP
EU
AC
C89
3S
KB
R3
MD
AM
B13
4VI
ZR
75B
BT
483
SU
M18
5PE
MD
AM
B41
5
Cisplatin (DNA cross−linker)
−lo
g10
GI5
0 (M
)
3.5
4.0
4.5
5.0
5.5
6.0
Claudin−lowBasalERBB2AMPLuminal
HC
C38
HC
C13
95A
U56
5S
UM
52P
EH
CC
1806
ZR
75B
UA
CC
812
SK
BR
3B
T48
3S
UM
1315
MO
2Z
R75
1M
DA
MB
453
MD
AM
B23
1H
CC
2185
SU
M18
5PE
MD
AM
B36
1M
DA
MB
436
MD
AM
B13
4VI
MD
AM
B41
5H
CC
1143 LY2
CA
MA
1M
DA
MB
157
HC
C20
2H
CC
3153
HC
C19
54M
CF
760
0MP
EH
CC
1428
HC
C14
19H
CC
1187
MD
AM
B46
8S
UM
159P
TH
CC
70U
AC
C89
3M
DA
MB
175V
IIZ
R75
30B
T47
4
CPT−11 (Topoisomerase I)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5
Claudin−lowERBB2AMPLuminalBasal
HC
C19
54S
UM
149P
TS
UM
52P
EH
CC
38H
CC
1187
HC
C18
06M
DA
MB
231
MD
AM
B41
5M
DA
MB
468
SU
M13
15M
O2
HC
C21
85U
AC
C81
2H
CC
202
ZR
7530 LY
2M
DA
MB
453
SU
M15
9PT
HC
C70
AU
565
HC
C13
95C
AM
A1
MD
AM
B36
1B
T47
4S
KB
R3
HC
C31
53H
CC
1143
UA
CC
893
MC
F7
ZR
75B
MD
AM
B17
5VII
HC
C14
19M
DA
MB
436
BT
483
MD
AM
B13
4VI
ZR
751
600M
PE
SU
M18
5PE
HC
C14
28
Docetaxel (Microtubule )
−lo
g10
GI5
0 (M
)
56
78
9
ERBB2AMPBasalLuminalClaudin−low
HC
C21
85H
CC
38U
AC
C81
2A
U56
5S
UM
52P
EZ
R75
30S
KB
R3
HC
C11
87Z
R75
1B
T48
3H
CC
1806
HC
C19
54 LY2
SU
M13
15M
O2
MD
AM
B45
3M
DA
MB
231
MD
AM
B36
1Z
R75
BH
CC
1395
CA
MA
160
0MP
EB
T47
4S
UM
185P
ES
UM
159P
TH
CC
3153
MD
AM
B41
5M
DA
MB
157
MC
F7
HC
C14
19H
CC
1143
HC
C20
2M
DA
MB
436
MD
AM
B17
5VII
MD
AM
B46
8U
AC
C89
3H
CC
1428
MD
AM
B13
4VI
HC
C70
Doxorubicin (Topoisomerase II)
−lo
g10
GI5
0 (M
)
5.0
5.5
6.0
6.5
7.0
7.5
LuminalClaudin−lowERBB2AMPBasal
SU
M13
15M
O2
HC
C38
MD
AM
B17
5VII
ZR
75B
HC
C21
85S
UM
159P
TA
U56
5B
T48
3H
CC
1806
HC
C19
54B
T54
9H
CC
1937 LY2
SU
M14
9PT
MD
AM
B45
3M
DA
MB
361
UA
CC
812
ZR
751
MD
AM
B41
5M
DA
MB
231
HC
C11
43S
UM
52P
E60
0MP
EM
CF
7S
UM
185P
EH
CC
70H
CC
1395
MD
AM
B15
7H
CC
202
HC
C31
53M
DA
MB
468
HC
C14
19M
DA
MB
436
UA
CC
893
HC
C11
87M
DA
MB
134V
IH
CC
1428
BT
474
Epirubicin (Topoisomerase II)
−lo
g10
GI5
0 (M
)
5.0
5.5
6.0
6.5
7.0
7.5
8.0
Claudin−lowLuminalERBB2AMPBasal
HC
C70
SU
M14
9PT
BT
20H
CC
1954
MD
AM
B17
5VII
HC
C18
06S
UM
225C
WN
SU
M13
15M
O2
HC
C11
87B
T47
4H
CC
1419
SU
M15
9PT
UA
CC
812
UA
CC
893
AU
565
SK
BR
3H
CC
1428
MD
AM
B46
8H
CC
2185
SU
M52
PE
HC
C31
53 LY2
HC
C20
2H
CC
1937
HC
C13
95M
DA
MB
231
BT
549
MD
AM
B45
3M
DA
MB
157
T47
D60
0MP
EM
DA
MB
436
HC
C11
43M
DA
MB
361
MD
AM
B13
4VI
SU
M18
5PE
CA
MA
1H
CC
38M
CF
7B
T48
3Z
R75
1Z
R75
B
Erlotinib (EGFR)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0 Basal
ERBB2AMPLuminalClaudin−low
SU
M13
15M
O2
HC
C38
AU
565
HC
C11
87S
UM
159P
TZ
R75
BH
CC
202
MD
AM
B15
7H
CC
1954
MD
AM
B43
6T
47D
SK
BR
3B
T54
9M
DA
MB
231
ZR
751
MD
AM
B13
4VI
MD
AM
B46
8S
UM
52P
ES
UM
149P
TH
CC
3153
HC
C13
95H
CC
1806
BT
20B
T48
3H
CC
1937
SU
M18
5PE
CA
MA
1M
DA
MB
453
HC
C11
43H
CC
2185
600M
PE
SU
M22
5CW
NM
CF
7H
CC
70M
DA
MB
415
MD
AM
B36
1B
T47
4H
CC
1428
UA
CC
893
HC
C14
19M
DA
MB
175V
II
Etoposide (Topoisomerase II)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5
7.0
Claudin−lowERBB2AMPBasalLuminal
LY2
HC
C11
87H
CC
1428
HC
C20
2S
UM
185P
EM
DA
MB
415
BT
483
SU
M22
5CW
NM
DA
MB
468
MD
AM
B36
1M
DA
MB
453
AU
565
HC
C70
HC
C21
85M
DA
MB
157
SU
M52
PE
UA
CC
893
MD
AM
B17
5VII
BT
474
MC
F7
SK
BR
3M
DA
MB
134V
IC
AM
A1
MD
AM
B23
1H
CC
1806
HC
C14
19H
CC
1954
HC
C38
HC
C11
4360
0MP
EB
T20
HC
C13
95H
CC
3153
ZR
751
HC
C19
37S
UM
149P
TZ
R75
BS
UM
1315
MO
2M
DA
MB
436
SU
M15
9PT
T47
DB
T54
9
Fascaplysin (CDK)
−lo
g10
GI5
0 (M
)
6.0
6.5
7.0
7.5
8.0
8.5 Luminal
BasalERBB2AMPClaudin−low
MD
AM
B17
5VII
HC
C20
2B
T47
4A
U56
5U
AC
C89
3H
CC
1954
HC
C14
19S
KB
R3
SU
M14
9PT
SU
M13
15M
O2
HC
C18
06B
T48
3M
DA
MB
361
HC
C13
9560
0MP
EM
DA
MB
453
MD
AM
B41
5S
UM
52P
EH
CC
1937
SU
M15
9PT
HC
C21
85H
CC
1428
HC
C11
43M
DA
MB
157
BT
549
T47
DH
CC
70S
UM
185P
EZ
R75
BM
DA
MB
468
MC
F7
CA
MA
1LY
2H
CC
38M
DA
MB
134V
IH
CC
1187
ZR
751
MD
AM
B43
6H
CC
3153
MD
AM
B23
1
Gefitinib (EGFR)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5
7.0 Luminal
ERBB2AMPBasalClaudin−low
HC
C20
2B
T54
9S
UM
149P
TS
UM
159P
TZ
R75
30H
CC
1954
UA
CC
893
SU
M52
PE
UA
CC
812
BT
474
HC
C11
87S
KB
R3
MD
AM
B17
5VII
HC
C21
85M
DA
MB
453
SU
M18
5PE
MD
AM
B13
4VI
MD
AM
B36
1M
DA
MB
468
HC
C38
MD
AM
B23
1H
CC
1937
HC
C14
28H
CC
1419
SU
M13
15M
O2
600M
PE
AU
565
MD
AM
B41
5H
CC
1395
HC
C31
53H
CC
1806
CA
MA
1H
CC
1143
HC
C70
ZR
75B
LY2
ZR
751
BT
483
MD
AM
B43
6M
CF
7
Geldanamycin (Hsp90)
−lo
g10
GI5
0 (M
)
6.0
6.5
7.0
7.5
8.0
8.5
9.0
9.5
ERBB2AMPClaudin−lowBasalLuminal
HC
C18
06M
DA
MB
361
BT
549
HC
C38
SU
M52
PE
MD
AM
B17
5VII
BT
483
MD
AM
B23
1S
UM
159P
TS
KB
R3
HC
C11
43S
UM
149P
TM
DA
MB
453
AU
565
600M
PE
HC
C21
85Z
R75
1LY
2M
DA
MB
436
ZR
75B
MD
AM
B46
8H
CC
3153
CA
MA
1H
CC
1187
SU
M18
5PE
HC
C13
95H
CC
1937
T47
DM
DA
MB
415
HC
C20
2H
CC
1428
MC
F7
HC
C70
BT
474
HC
C14
19U
AC
C89
3H
CC
1954
Gemcitabine (pyrimidine animetabolite)
−lo
g10
GI5
0 (M
)
45
67
89 Basal
ERBB2AMPClaudin−lowLuminal
HC
C70
HC
C11
87
HC
C38
MD
AM
B13
4VI
SU
M15
9PT
MD
AM
B46
8
HC
C21
85
ZR
751
BT
20
AU
565
CA
MA
1
SU
M52
PE
SU
M13
15M
O2
T47
D
HC
C11
43
HC
C14
19
MC
F7
MD
AM
B23
1
MD
AM
B45
3
SU
M14
9PT
HC
C31
53
MD
AM
B36
1
MD
AM
B17
5VII
HC
C19
54
MD
AM
B41
5
UA
CC
812
MD
AM
B43
6
BT
483
SK
BR
3
HC
C14
28
BT
474
HC
C19
37
ZR
75B
Glycyl−H−1152 (Rho kinase)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5
BasalClaudin−lowLuminalERBB2AMP
HC
C20
2S
UM
185P
EH
CC
2185
SU
M52
PE
UA
CC
893
ZR
7530
BT
474
HC
C70
SU
M15
9PT
SK
BR
3H
CC
1954
UA
CC
812
HC
C14
19T
47D
MD
AM
B45
3Z
R75
BS
UM
1315
MO
2H
CC
1187
AU
565
600M
PE
HC
C14
28H
CC
1143
MD
AM
B13
4VI
MD
AM
B17
5VII
HC
C38
HC
C19
37S
UM
149P
TM
DA
MB
468
MD
AM
B43
6Z
R75
1M
DA
MB
361
LY2
HC
C18
06C
AM
A1
BT
549
HC
C13
95M
CF
7H
CC
3153
MD
AM
B23
1
GSK1059615 ()
−lo
g10
GI5
0 (M
)
5.0
5.5
6.0
6.5
7.0
7.5
ERBB2AMPLuminalBasalClaudin−low
HC
C11
87M
DA
MB
468
MD
AM
B43
6S
UM
52P
EH
CC
70H
CC
38H
CC
2185
HC
C13
95H
CC
202
MD
AM
B15
7S
UM
185P
ES
UM
1315
MO
2M
DA
MB
231
SU
M15
9PT
MD
AM
B41
5Z
R75
BM
DA
MB
134V
IH
CC
1954
AU
565
MD
AM
B45
3H
CC
1143
SU
M14
9PT
HC
C19
37B
T48
3S
KB
R3
BT
474
HC
C14
28M
DA
MB
361
HC
C14
19H
CC
1806
600M
PE
MD
AM
B17
5VII
UA
CC
893
MC
F7
CA
MA
1H
CC
3153
ZR
751
ZR
7530
UA
CC
812
GSK1070916 (aurora kinase B &C)
−lo
g10
GI5
0 (M
)
45
67
8
BasalClaudin−lowLuminalERBB2AMP
HC
C20
2H
CC
7060
0MP
EM
DA
MB
175V
IIS
UM
159P
TM
DA
MB
134V
IS
UM
149P
TH
CC
1419
SU
M13
15M
O2
MD
AM
B23
1H
CC
1395
MD
AM
B45
3H
CC
1954
MD
AM
B41
5B
T54
9H
CC
1806
SU
M52
PE
MD
AM
B46
8A
U56
5M
DA
MB
436
UA
CC
893
SU
M18
5PE
MD
AM
B15
7B
T47
4H
CC
1187
HC
C21
85H
CC
3153
CA
MA
1H
CC
1937
HC
C38
MD
AM
B36
1U
AC
C81
2M
CF
7LY
2B
T48
3S
KB
R3
ZR
751
ZR
75B
HC
C14
28T
47D
GSK1120212 ()
−lo
g10
GI5
0 (M
)
56
78
910
ERBB2AMPBasalLuminalClaudin−low
UA
CC
893
HC
C20
2
MD
AM
B46
8
HC
C19
54
UA
CC
812
SU
M52
PE
HC
C21
85
SU
M13
15M
O2
MD
AM
B13
4VI
SU
M15
9PT
MD
AM
B23
1
AU
565
HC
C38
HC
C11
87
HC
C14
28
HC
C70
SK
BR
3
MD
AM
B45
3
HC
C31
53
CA
MA
1
ZR
751
BT
483
BT
549
MD
AM
B36
1
SU
M14
9PT
MD
AM
B15
7
HC
C18
06
MD
AM
B41
5
MC
F7
LY2
T47
D
MD
AM
B17
5VII
BT
20
GSK1487371 ()
−lo
g10
GI5
0 (M
)
45
67
89
10
LuminalERBB2AMPBasalClaudin−low
600M
PE
LY2
MC
F7
HC
C14
28S
UM
52P
EA
U56
5H
CC
1187
HC
C11
43H
CC
2185
BT
483
SU
M18
5PE
SU
M15
9PT
SU
M14
9PT
MD
AM
B41
5S
UM
1315
MO
2U
AC
C81
2M
DA
MB
175V
IIM
DA
MB
468
MD
AM
B23
1H
CC
1395
HC
C31
53H
CC
1419
BT
549
UA
CC
893
HC
C70
ZR
751
SK
BR
3H
CC
202
BT
474
HC
C19
54M
DA
MB
453
MD
AM
B13
4VI
MD
AM
B15
7C
AM
A1
MD
AM
B36
1T
47D
ZR
75B
MD
AM
B43
6H
CC
38S
UM
225C
WN
HC
C19
37B
T20
HC
C18
06
GSK1838705 ()
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5
7.0
LuminalERBB2AMPBasalClaudin−low
HC
C20
2S
UM
52P
EB
T48
3H
CC
1419
T47
DU
AC
C81
2B
T47
4S
KB
R3
UA
CC
893
SU
M15
9PT
MD
AM
B45
3LY
2M
DA
MB
134V
IA
U56
5S
UM
1315
MO
260
0MP
EH
CC
1187
HC
C70
HC
C38
MC
F7
HC
C14
28H
CC
1954
BT
20M
DA
MB
175V
IIM
DA
MB
468
HC
C18
06S
UM
149P
TZ
R75
BM
DA
MB
361
ZR
751
HC
C19
37M
DA
MB
436
HC
C11
43B
T54
9H
CC
1395
MD
AM
B23
1C
AM
A1
MD
AM
B15
7H
CC
3153
GSK2119563 ()
−lo
g10
GI5
0 (M
)
45
67
8 ERBB2AMPLuminalClaudin−lowBasal
HC
C20
2B
T48
3H
CC
1419
UA
CC
812
SU
M52
PE
T47
DS
KB
R3
BT
474
ZR
75B
HC
C11
87M
DA
MB
175V
IIM
DA
MB
453
600M
PE
UA
CC
893
MC
F7
HC
C70
AU
565
ZR
751
SU
M13
15M
O2
HC
C19
54M
DA
MB
134V
ILY
2B
T20
SU
M14
9PT
HC
C38
HC
C19
37H
CC
1806
SU
M15
9PT
HC
C14
28M
DA
MB
468
MD
AM
B36
1H
CC
1143
HC
C31
53B
T54
9H
CC
1395
CA
MA
1M
DA
MB
436
MD
AM
B15
7M
DA
MB
231
GSK2126458 ()
−lo
g10
GI5
0 (M
)
56
78
9
ERBB2AMPLuminalBasalClaudin−low
MD
AM
B15
7M
DA
MB
361
MD
AM
B46
8A
U56
5H
CC
1395
HC
C21
85S
UM
52P
EH
CC
1954
UA
CC
893
MD
AM
B45
3H
CC
1806
MD
AM
B43
6M
DA
MB
134V
IM
CF
7S
KB
R3
SU
M14
9PT
MD
AM
B23
1H
CC
1937
SU
M13
15M
O2
HC
C31
53S
UM
159P
TH
CC
1187
HC
C38
HC
C11
43M
DA
MB
415
ZR
75B
HC
C70
SU
M18
5PE
BT
483
HC
C14
28M
DA
MB
175V
IIZ
R75
30C
AM
A1
600M
PE
HC
C14
19B
T47
4U
AC
C81
2Z
R75
1H
CC
202
GSK461364 ()
−lo
g10
GI5
0 (M
)
45
67
89
Claudin−lowERBB2AMPBasalLuminal
UA
CC
812
UA
CC
893
HC
C20
2H
CC
70Z
R75
30S
UM
52P
EH
CC
1954
AU
565
MD
AM
B46
8M
DA
MB
436
HC
C11
87M
DA
MB
157
SU
M13
15M
O2
SU
M15
9PT
HC
C21
85M
DA
MB
361
HC
C18
06M
DA
MB
231
SK
BR
3H
CC
1395
CA
MA
1H
CC
38M
DA
MB
415
HC
C31
53H
CC
1937
SU
M14
9PT
ZR
75B
MD
AM
B45
3Z
R75
1H
CC
1143
MD
AM
B17
5VII
BT
483
MC
F7
HC
C14
19M
DA
MB
134V
IS
UM
185P
EB
T47
4H
CC
1428
600M
PE
GSK923295 (CENPE)
−lo
g10
GI5
0 (M
)
45
67
8
ERBB2AMPLuminalBasalClaudin−low
HC
C13
95
HC
C14
19
HC
C21
85
BT
20
HC
C18
06
MD
AM
B17
5VII
T47
D
SU
M52
PE
HC
C19
37
SU
M15
9PT
HC
C11
43
MD
AM
B41
5
SU
M13
15M
O2
HC
C19
54
HC
C38
BT
483
MD
AM
B13
4VI
HC
C70
ZR
751
MD
AM
B23
1
HC
C31
53
SK
BR
3
MD
AM
B46
8
BT
474
MD
AM
B45
3
HC
C14
28
ZR
75B
UA
CC
812
CA
MA
1
HC
C11
87
SU
M14
9PT
AU
565
SU
M22
5CW
N
Ibandronate sodium salt (farnesyl diphosphate synthase)
−lo
g10
GI5
0 (M
)
3.0
3.5
4.0
4.5
5.0
5.5
Claudin−lowERBB2AMPLuminalBasal
ZR
75B
HC
C38
SU
M15
9PT
SU
M13
15M
O2
AU
565
ZR
751
HC
C11
87
HC
C21
85
SU
M52
PE
SK
BR
3
MD
AM
B46
8
HC
C19
54
SU
M14
9PT
UA
CC
812
HC
C31
53
MD
AM
B36
1
MD
AM
B17
5VII
HC
C70
MC
F7
LY2
T47
D
MD
AM
B41
5
MD
AM
B45
3
MD
AM
B13
4VI
HC
C14
28
BT
20
MD
AM
B43
6
BT
474
CA
MA
1
HC
C19
37
HC
C11
43
HC
C18
06
ICRF−193 (PLK1, topo II)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5
7.0
LuminalClaudin−lowERBB2AMPBasal
BT
483
HC
C20
2U
AC
C89
3B
T20
MD
AM
B46
860
0MP
EA
U56
5LY
2H
CC
1187
HC
C13
95H
CC
3153
HC
C18
06S
UM
52P
EH
CC
2185
HC
C19
54C
AM
A1
MD
AM
B15
7M
DA
MB
231
SU
M14
9PT
SK
BR
3M
DA
MB
361
MC
F7
MD
AM
B43
6S
UM
1315
MO
2M
DA
MB
453
MD
AM
B13
4VI
HC
C70
BT
549
HC
C38
SU
M15
9PT
BT
474
HC
C11
43M
DA
MB
415
T47
DZ
R75
1S
UM
225C
WN
SU
M18
5PE
ZR
75B
HC
C19
37M
DA
MB
175V
IIH
CC
1428
HC
C14
19
Ispinesib (Kinesin)
−lo
g10
GI5
0 (M
)
56
78
910
11
LuminalERBB2AMPBasalClaudin−low
MC
F7
MD
AM
B23
1C
AM
A1
MD
AM
B46
8H
CC
70M
DA
MB
134V
IH
CC
1954
HC
C11
87M
DA
MB
361
HC
C38
SU
M52
PE
AU
565
MD
AM
B15
7H
CC
1806
SU
M14
9PT
MD
AM
B43
6LY
2B
T54
9S
UM
1315
MO
2H
CC
3153
UA
CC
893
SU
M15
9PT
MD
AM
B45
3T
47D
MD
AM
B41
5B
T20
BT
474
SU
M18
5PE
HC
C11
43S
KB
R3
HC
C13
95H
CC
1428
ZR
751
HC
C19
3760
0MP
EB
T48
3U
AC
C81
2H
CC
2185
HC
C14
19H
CC
202
SU
M22
5CW
N
Ixabepilone (Microtubule )
−lo
g10
GI5
0 (M
)
45
67
89
10 LuminalClaudin−lowBasalERBB2AMP
MD
AM
B43
6
SU
M14
9PT
SU
M52
PE
HC
C11
87
MD
AM
B17
5VII
MD
AM
B36
1
UA
CC
812
MD
AM
B46
8
BT
483
HC
C19
37
HC
C14
28
HC
C14
19
HC
C38
BT
474
SU
M15
9PT
SK
BR
3
SU
M13
15M
O2
MD
AM
B13
4VI
HC
C13
95
ZR
751
ZR
75B
HC
C70
MD
AM
B23
1
HC
C31
53
MD
AM
B45
3
MC
F7
HC
C19
54
AU
565
T47
D
CA
MA
1
BT
20
HC
C21
85
HC
C11
43
L−779450 (B−raf)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0 Claudin−low
BasalLuminalERBB2AMP
HC
C14
19B
T47
4A
U56
5U
AC
C81
2S
KB
R3
SU
M22
5CW
NH
CC
202
MD
AM
B17
5VII
UA
CC
893
HC
C19
54H
CC
2185
MD
AM
B45
3M
DA
MB
361
HC
C70
SU
M13
15M
O2
T47
DM
DA
MB
436
MD
AM
B15
7H
CC
1395
HC
C11
87H
CC
3153
CA
MA
1H
CC
1937
HC
C11
43M
DA
MB
468
HC
C38
BT
549
MD
AM
B23
160
0MP
EM
CF
7S
UM
52P
EB
T48
3Z
R75
1H
CC
1806
ZR
75B
HC
C14
28B
T20
Lapatinib (ERBB2, EGFR)
−lo
g10
GI5
0 (M
)
4.5
5.0
5.5
6.0
6.5
7.0
ERBB2AMPLuminalBasalClaudin−low
BT
474
HC
C38
MD
AM
B41
5M
DA
MB
453
MD
AM
B36
1S
KB
R3
HC
C14
19C
AM
A1
MD
AM
B13
4VI
HC
C21
85B
T48
3S
UM
185P
EH
CC
70M
CF
7H
CC
1143
ZR
75B
AU
565
UA
CC
812
SU
M15
9PT
HC
C14
28T
47D
HC
C18
06S
UM
52P
EH
CC
1187
600M
PE
HC
C19
37Z
R75
1M
DA
MB
468
SU
M13
15M
O2
MD
AM
B43
6H
CC
3153
SU
M14
9PT
HC
C19
54B
T20
MD
AM
B17
5VII
LBH589 (HDAC, pan inibitor)
−lo
g10
GI5
0 (M
)
6.0
6.5
7.0
7.5
8.0 ERBB2AMP
Claudin−lowLuminalBasal
SU
M13
15M
O2
HC
C38
SU
M18
5PE
SU
M14
9PT
SU
M52
PE
HC
C18
06H
CC
70B
T47
4S
UM
159P
TH
CC
1143
MD
AM
B13
4VI
MD
AM
B46
8Z
R75
BM
DA
MB
361
HC
C14
28H
CC
1937
MD
AM
B45
3B
T48
3M
DA
MB
175V
IIH
CC
1187
AU
565
SU
M22
5CW
NS
KB
R3
UA
CC
812
HC
C14
19M
DA
MB
436
MC
F7
600M
PE
ZR
751
CA
MA
1H
CC
2185
BT
20H
CC
1954
T47
DH
CC
3153
Lestaurtinib (FLT−3, TrkA)
−lo
g10
GI5
0 (M
)
5.0
5.5
6.0
6.5
7.0
7.5
8.0
Claudin−lowLuminalBasalERBB2AMP
HC
C19
54M
DA
MB
436
HC
C20
2H
CC
1143
MD
AM
B46
8LY
2M
CF
7Z
R75
1C
AM
A1
MD
AM
B36
1S
KB
R3
HC
C18
06H
CC
1187
MD
AM
B15
760
0MP
EH
CC
1419
AU
565
MD
AM
B13
4VI
SU
M18
5PE
HC
C13
95B
T47
4S
UM
1315
MO
2H
CC
2185
HC
C19
37H
CC
38B
T54
9M
DA
MB
231
MD
AM
B45
3S
UM
149P
TS
UM
52P
ES
UM
159P
TZ
R75
BH
CC
1428
BT
20S
UM
225C
WN
MD
AM
B41
5
Methotrexate (DHFR)
−lo
g10
GI5
0 (M
)
45
67
8 ERBB2AMPClaudin−lowBasalLuminal
HC
C18
06
HC
C14
19
HC
C38
CA
MA
1
MD
AM
B13
4VI
MD
AM
B41
5
HC
C14
28
T47
D
ZR
75B
SK
BR
3
LY2
AU
565
SU
M14
9PT
MD
AM
B46
8
HC
C31
53
HC
C11
43
MD
AM
B43
6
600M
PE
HC
C21
85
SU
M52
PE
MD
AM
B17
5VII
HC
C11
87
BT
474
SU
M15
9PT
UA
CC
812
MD
AM
B45
3
HC
C19
37
BT
20
HC
C19
54
SU
M13
15M
O2
BT
483
HC
C70
ZR
751
MLN4924 (NAE)
−lo
g10
GI5
0 (M
)
45
67
8 BasalERBB2AMPClaudin−lowLuminal
SU
M18
5PE
LY2
HC
C13
95H
CC
1937
BT
483
SU
M13
15M
O2
HC
C21
85S
KB
R3
AU
565
SU
M14
9PT
ZR
751
HC
C31
53H
CC
1419
HC
C11
43H
CC
1187
SU
M22
5CW
NS
UM
159P
TH
CC
38S
UM
52P
EH
CC
1428
MD
AM
B41
5C
AM
A1
BT
474
HC
C70
BT
20M
CF
7U
AC
C81
260
0MP
EM
DA
MB
453
ZR
75B
MD
AM
B13
4VI
HC
C19
54M
DA
MB
175V
IIT
47D
MD
AM
B46
8M
DA
MB
361
NSC 663284 (cdc25s)
−lo
g10
GI5
0 (M
)
5.0
5.5
6.0
6.5
7.0
LuminalClaudin−lowBasalERBB2AMP
SU
M18
5PE
SU
M13
15M
O2
SU
M52
PE
HC
C13
95H
CC
1187
SU
M14
9PT
HC
C38
MD
AM
B45
3C
AM
A1
SU
M15
9PT
HC
C14
28H
CC
1143
MD
AM
B46
8Z
R75
BH
CC
2185
T47
DH
CC
3153
MD
AM
B36
1Z
R75
1H
CC
70A
U56
5H
CC
1806
BT
474
HC
C14
19S
KB
R3
MD
AM
B41
5U
AC
C81
2M
CF
7H
CC
1954
MD
AM
B13
4VI
LY2
SU
M22
5CW
NM
DA
MB
436
HC
C19
37M
DA
MB
175V
IIB
T20
BT
483
NU6102 (CDK1/CCNB)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
LuminalClaudin−lowBasalERBB2AMP
ZR
75B
ZR
751
LY2
MC
F7
BT
483
MD
AM
B17
5VII
HC
C20
2H
CC
2185
AU
565
SU
M15
9PT
MD
AM
B13
4VI
HC
C19
54H
CC
70S
UM
52P
ES
UM
225C
WN
UA
CC
893
HC
C11
87S
UM
1315
MO
2H
CC
1143
HC
C38
HC
C13
95H
CC
1937
MD
AM
B41
5S
UM
149P
TS
UM
185P
ET
47D
HC
C14
28B
T20
UA
CC
812
MD
AM
B15
7H
CC
3153
MD
AM
B46
8H
CC
1419
BT
474
BT
549
600M
PE
SK
BR
3M
DA
MB
453
CA
MA
1M
DA
MB
436
HC
C18
06M
DA
MB
361
MD
AM
B23
1
Nutlin 3a (MDM2)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0 Luminal
ERBB2AMPClaudin−lowBasal
SU
M14
9PT
UA
CC
812
HC
C11
87B
T54
9Z
R75
1S
UM
159P
TH
CC
1806
SK
BR
3H
CC
1954
AU
565
HC
C21
85Z
R75
BT
47D
MD
AM
B36
1M
DA
MB
175V
IIH
CC
38S
UM
52P
EH
CC
70H
CC
1937
MC
F7
MD
AM
B45
3H
CC
202
LY2
HC
C31
53H
CC
1428
CA
MA
1H
CC
1395
600M
PE
SU
M13
15M
O2
HC
C14
19B
T47
4M
DA
MB
231
HC
C11
43B
T48
3M
DA
MB
157
MD
AM
B41
5S
UM
185P
EM
DA
MB
468
MD
AM
B43
6U
AC
C89
3Z
R75
30
Oxaliplatin (DNA cross−linker)
−lo
g10
GI5
0 (M
)
3.0
3.5
4.0
4.5
5.0
5.5
6.0
BasalERBB2AMPClaudin−lowLuminal
HC
C38
BT
474
MD
AM
B45
3S
UM
185P
ES
UM
159P
TH
CC
2185
ZR
75B
HC
C70
HC
C14
28H
CC
1143
CA
MA
1S
UM
52P
EA
U56
5H
CC
1187
MD
AM
B13
4VI
SU
M14
9PT
HC
C18
06M
DA
MB
361
BT
483
MD
AM
B41
5S
UM
225C
WN
T47
DS
KB
R3
LY2
HC
C14
19H
CC
1937
HC
C31
53H
CC
1954
MC
F7
UA
CC
812
ZR
751
HC
C13
95S
UM
1315
MO
2M
DA
MB
468
BT
20M
DA
MB
175V
IIM
DA
MB
436
Oxamflatin (HDAC)
−lo
g10
GI5
0 (M
)
5.0
5.5
6.0
6.5
7.0
Claudin−lowERBB2AMPLuminalBasal
SU
M52
PE
MD
AM
B23
1M
DA
MB
415
SU
M13
15M
O2
HC
C19
54H
CC
2185
HC
C38
ZR
75B
HC
C20
2H
CC
70A
U56
5H
CC
1806
MD
AM
B46
8H
CC
1187
UA
CC
812
SU
M14
9PT
MD
AM
B13
4VI
BT
474
MD
AM
B45
3LY
2C
AM
A1
SK
BR
3U
AC
C89
3M
DA
MB
361
SU
M15
9PT
HC
C13
95M
CF
7H
CC
1143
MD
AM
B17
5VII
HC
C31
53Z
R75
30S
UM
185P
EZ
R75
1B
T48
3M
DA
MB
436
600M
PE
HC
C14
19H
CC
1428
Paclitaxel (Microtubule )
−lo
g10
GI5
0 (M
)
45
67
89
LuminalClaudin−lowERBB2AMPBasal
HC
C11
87
AU
565
SU
M52
PE
SU
M18
5PE
SK
BR
3
CA
MA
1
HC
C21
85
HC
C19
37
SU
M14
9PT
SU
M22
5CW
N
ZR
751
MD
AM
B46
8
SU
M13
15M
O2
MD
AM
B36
1
HC
C70
600M
PE
HC
C18
06
SU
M15
9PT
HC
C19
54
T47
D
UA
CC
812
MD
AM
B17
5VII
HC
C14
19
MD
AM
B13
4VI
BT
483
HC
C14
28
BT
20
HC
C13
95
BT
474
HC
C11
43
ZR
75B
PD 98059 (MEK)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
BasalERBB2AMPLuminalClaudin−low
SU
M52
PE
HC
C13
95M
DA
MB
453
MD
AM
B15
7H
CC
38S
UM
1315
MO
2H
CC
1419
HC
C18
06M
DA
MB
436
SU
M15
9PT
MD
AM
B46
8H
CC
1428
MD
AM
B23
1U
AC
C89
3H
CC
70U
AC
C81
2B
T54
9LY
2A
U56
5H
CC
1937
HC
C19
54S
KB
R3
HC
C20
2S
UM
149P
T60
0MP
EH
CC
1187
HC
C11
43T
47D
MD
AM
B36
1H
CC
3153
ZR
751
BT
20M
DA
MB
134V
IH
CC
2185
BT
474
PD173074 (FGFR3)
−lo
g10
GI5
0 (M
)
45
67
8 LuminalClaudin−lowERBB2AMPBasal
HC
C20
2
HC
C19
54 LY2
MD
AM
B36
1
MD
AM
B45
3
HC
C19
37
ZR
751
HC
C18
06
SK
BR
3
CA
MA
1
MD
AM
B46
8
MD
AM
B13
4VI
SU
M18
5PE
MD
AM
B43
6
MD
AM
B15
7
BT
474
HC
C11
87
SU
M13
15M
O2
HC
C21
85
HC
C31
53
HC
C11
43
HC
C38
BT
549
HC
C14
19
UA
CC
812
HC
C70
MC
F7
SU
M52
PE
BT
483
HC
C14
28
AU
565
T47
D
Pemetrexed (DNA synthesis/repair)
−lo
g10
GI5
0 (M
)
34
56
7
ERBB2AMPLuminalBasalClaudin−low
SU
M13
15M
O2
AU
565
HC
C19
37S
UM
149P
TM
CF
7S
UM
52P
EH
CC
1187
SU
M18
5PE
SK
BR
3H
CC
2185
BT
2060
0MP
EM
DA
MB
175V
IIH
CC
1428
HC
C19
54B
T48
3S
UM
225C
WN
MD
AM
B13
4VI
MD
AM
B46
8Z
R75
1H
CC
1806
HC
C20
2C
AM
A1
HC
C31
53M
DA
MB
436
MD
AM
B15
7H
CC
1395
BT
474
UA
CC
893
HC
C11
43B
T54
9M
DA
MB
231
HC
C14
19M
DA
MB
361
HC
C70
SU
M15
9PT
ZR
75B
T47
D
Purvalanol A (CDK1)
−lo
g10
GI5
0 (M
)
3.5
4.0
4.5
5.0
Claudin−lowERBB2AMPBasalLuminal
SU
M44
PE
HC
C21
85B
T48
3M
DA
MB
415
SU
M52
PE
HC
C19
54M
DA
MB
175V
IIH
CC
1419
HC
C20
2M
DA
MB
134V
IB
T20
CA
MA
1B
T47
4S
UM
225C
WN
AU
565
HC
C11
87H
CC
38U
AC
C81
2H
CC
1428
SK
BR
3H
CC
70M
CF
7T
47D
SU
M15
9PT
MD
AM
B36
1H
CC
1937
MD
AM
B46
8S
UM
1315
MO
2M
DA
MB
231
HC
C31
53S
UM
149P
TB
T54
9H
CC
1806
MD
AM
B43
6M
DA
MB
157
UA
CC
893
Rapamycin (mTOR)
−lo
g10
GI5
0 (M
)
45
67
89
LuminalERBB2AMPBasalClaudin−low
BT
474
SU
M15
9PT
HC
C11
87S
UM
185P
EH
CC
38Z
R75
BB
T48
3S
UM
149P
TB
T20
UA
CC
812
SU
M52
PE
HC
C21
85H
CC
1428
MD
AM
B13
4VI
HC
C31
53C
AM
A1
HC
C19
37H
CC
1143
MD
AM
B46
8M
DA
MB
361
MD
AM
B17
5VII
MC
F7
SK
BR
3Z
R75
1H
CC
1806
HC
C19
54A
U56
5T
47D
SU
M22
5CW
NM
DA
MB
415
SU
M13
15M
O2
HC
C70
MD
AM
B43
6H
CC
1395
MD
AM
B23
1H
CC
1419
MD
AM
B45
3
SB−3CT (MMP2, MMP9)
−lo
g10
GI5
0 (M
)
3.5
4.0
4.5
5.0
ERBB2AMPClaudin−lowBasalLuminal
BT
483
BT
474
SU
M22
5CW
NM
DA
MB
361
HC
C14
19S
UM
185P
EZ
R75
1Z
R75
BS
UM
52P
ET
47D
MC
F7
LY2
HC
C21
85H
CC
70M
DA
MB
453
SK
BR
3A
U56
5C
AM
A1
UA
CC
812
MD
AM
B17
5VII
HC
C11
87H
CC
1428
SU
M13
15M
O2
SU
M15
9PT
HC
C19
54H
CC
1806
SU
M14
9PT
MD
AM
B13
4VI
MD
AM
B46
8B
T20
HC
C19
37H
CC
3153
HC
C38
MD
AM
B41
5H
CC
1143
MD
AM
B43
6
Sigma AKT1−2 inhibitor (Akt 1/2)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5 Luminal
ERBB2AMPBasalClaudin−low
SU
M18
5PE
SU
M52
PE
BT
483
HC
C21
85S
UM
149P
TS
UM
159P
TT
47D
MD
AM
B13
4VI
HC
C11
87H
CC
70S
UM
225C
WN
ZR
751
600M
PE
HC
C14
28H
CC
1395
MD
AM
B43
6H
CC
1954
HC
C11
43M
DA
MB
361
BT
20M
CF
7S
KB
R3
HC
C20
2M
DA
MB
175V
IIH
CC
38M
DA
MB
231
CA
MA
1M
DA
MB
415
BT
474
BT
549
HC
C31
53H
CC
1806
MD
AM
B46
8A
U56
5S
UM
1315
MO
2M
DA
MB
157
UA
CC
893
HC
C14
19H
CC
1937
ZR
75B
MD
AM
B45
3
Sorafenib (VEGFR )
−lo
g10
GI5
0 (M
)
3.0
3.5
4.0
4.5
5.0
5.5
6.0 Luminal
BasalClaudin−lowERBB2AMP
UA
CC
893
SU
M18
5PE
SU
M52
PE
SU
M15
9PT
HC
C70
SU
M14
9PT
MD
AM
B23
1A
U56
5M
DA
MB
453
600M
PE
MD
AM
B46
8H
CC
1395
HC
C11
87H
CC
1428
BT
549
HC
C18
06M
DA
MB
175V
IIM
DA
MB
415
HC
C19
54H
CC
38M
CF
7M
DA
MB
157
SU
M22
5CW
NLY
2S
KB
R3
HC
C19
37H
CC
1143
SU
M13
15M
O2
ZR
75B
T47
DC
AM
A1
HC
C20
2M
DA
MB
134V
IH
CC
3153
MD
AM
B43
6M
DA
MB
361
ZR
751
BT
20B
T47
4H
CC
1419
BT
483
HC
C21
85
Sunitinib Malate (VEGFR )
−lo
g10
GI5
0 (M
)
4.5
5.0
5.5
6.0
6.5
LuminalClaudin−lowBasalERBB2AMP
BT
474
UA
CC
893
HC
C14
28S
UM
185P
EH
CC
1806
HC
C21
85M
DA
MB
175V
IIH
CC
1395
HC
C11
43Z
R75
BB
T48
3A
U56
5H
CC
202
MD
AM
B43
6H
CC
1419
MD
AM
B41
5C
AM
A1
MD
AM
B45
360
0MP
EH
CC
38 LY2
MD
AM
B13
4VI
SU
M52
PE
HC
C19
54S
UM
1315
MO
2M
CF
7S
UM
149P
TS
KB
R3
SU
M15
9PT
MD
AM
B15
7H
CC
3153
HC
C19
37B
T54
9M
DA
MB
231
MD
AM
B36
1H
CC
70Z
R75
1T
47D
Tamoxifen (ESR1)
−lo
g10
GI5
0 (M
)
3.5
4.0
4.5
5.0
5.5
6.0
ERBB2AMPLuminalBasalClaudin−low
HC
C13
95H
CC
38S
UM
185P
ELY
2S
UM
149P
TM
DA
MB
415
AU
565
MD
AM
B43
6H
CC
70H
CC
1937
SU
M13
15M
O2
HC
C11
43S
UM
52P
EH
CC
3153
MD
AM
B36
1M
DA
MB
453
SK
BR
3C
AM
A1
600M
PE
BT
474
BT
483
HC
C18
06S
UM
225C
WN
HC
C14
28Z
R75
1M
DA
MB
468
ZR
75B
SU
M15
9PT
HC
C11
87M
CF
7U
AC
C81
2H
CC
1419
T47
DH
CC
2185
MD
AM
B13
4VI
MD
AM
B17
5VII
BT
20H
CC
1954
TCS 2312 dihydrochloride (chk1)
−lo
g10
GI5
0 (M
)
5.0
5.5
6.0
6.5
7.0
7.5
Claudin−lowLuminalBasalERBB2AMP
SU
M13
15M
O2
HC
C13
95
MD
AM
B45
3
HC
C11
87
BT
20
BT
483
HC
C19
54
UA
CC
812
HC
C70
HC
C31
53
CA
MA
1
SU
M14
9PT
HC
C38
SK
BR
3
MD
AM
B17
5VII
SU
M52
PE
MD
AM
B13
4VI
HC
C21
85
HC
C14
28
ZR
75B
MD
AM
B46
8
HC
C11
43
BT
474
SU
M18
5PE
HC
C18
06
HC
C19
37
MD
AM
B43
6
TCS JNK 5a (JNK)
−lo
g10
GI5
0 (M
)
3.5
4.0
4.5
5.0
5.5
6.0
6.5 Claudin−low
LuminalBasalERBB2AMP
SU
M52
PE
SU
M18
5PE
HC
C21
85B
T47
4C
AM
A1
HC
C14
19S
KB
R3
MD
AM
B41
5M
DA
MB
453
AU
565
ZR
75B
MD
AM
B13
4VI
LY2
HC
C19
54S
UM
159P
TM
DA
MB
361
HC
C38
HC
C70
HC
C19
37U
AC
C81
2B
T20
HC
C11
87S
UM
1315
MO
2T
47D
MC
F7
HC
C11
43M
DA
MB
175V
IIM
DA
MB
468
HC
C14
28S
UM
149P
TH
CC
1395
600M
PE
HC
C31
53H
CC
1806
MD
AM
B43
6B
T48
3Z
R75
1
Temsirolimus (mTOR)
−lo
g10
GI5
0 (M
)
45
67
89
10
LuminalERBB2AMPClaudin−lowBasal
ZR
75B
MD
AM
B46
8H
CC
70Z
R75
1H
CC
1187
T47
DB
T48
3S
KB
R3
HC
C20
2A
U56
5H
CC
1419
HC
C13
95H
CC
38C
AM
A1
BT
474
600M
PE
SU
M13
15M
O2
UA
CC
812
MD
AM
B45
3H
CC
1954 LY2
MD
AM
B13
4VI
BT
20H
CC
1428
MD
AM
B36
1M
DA
MB
436
BT
549
MD
AM
B23
1S
UM
149P
TH
CC
1937
SU
M15
9PT
HC
C11
43H
CC
1806
HC
C31
53M
DA
MB
157
UA
CC
893
MD
AM
B17
5VII
TGX−221 (PI3K, beta selective)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5
LuminalBasalERBB2AMPClaudin−low
HC
C38
SU
M52
PE
SU
M13
15M
O2
SK
BR
3H
CC
1395
BT
483
AU
565
HC
C18
06M
DA
MB
436
ZR
751
HC
C21
85M
DA
MB
468
UA
CC
812
ZR
75B
SU
M18
5PE
MD
AM
B45
3M
DA
MB
134V
IM
DA
MB
415
HC
C31
53H
CC
1143 LY2
HC
C19
54H
CC
1187
UA
CC
893
HC
C14
19S
UM
44P
EC
AM
A1
MD
AM
B15
7H
CC
1428
MD
AM
B36
1S
UM
159P
TH
CC
202
MD
AM
B23
1M
CF
7B
T47
4M
DA
MB
175V
IIH
CC
70
Topotecan (Topoisomerase I)
−lo
g10
GI5
0 (M
)
56
78
9
Claudin−lowLuminalERBB2AMPBasal
SU
M52
PE
SU
M13
15M
O2
MD
AM
B46
8S
UM
159P
TS
UM
149P
TH
CC
1187
HC
C14
19H
CC
38H
CC
1428
HC
C70
HC
C21
85H
CC
1806
HC
C13
95U
AC
C89
3M
DA
MB
436
HC
C11
43H
CC
3153
MD
AM
B13
4VI
HC
C19
54 LY2
MD
AM
B23
1Z
R75
1B
T20
MD
AM
B15
7B
T47
4H
CC
1937
BT
549
MD
AM
B36
1M
DA
MB
453
600M
PE
SK
BR
3A
U56
5H
CC
202
T47
D
TPCA−1 (IKK2 (IkB kinase 2))
−lo
g10
GI5
0 (M
)
3.5
4.0
4.5
5.0
5.5
6.0
6.5 Luminal
Claudin−lowBasalERBB2AMP
HC
C20
2H
CC
1428
CA
MA
1S
UM
52P
EU
AC
C89
3T
47D
AU
565
HC
C11
87Z
R75
BM
DA
MB
231
MD
AM
B45
3M
DA
MB
175V
IIS
UM
159P
TH
CC
38S
KB
R3
600M
PE
MD
AM
B13
4VI
MC
F7
SU
M14
9PT
BT
549
MD
AM
B36
1U
AC
C81
2B
T47
4B
T48
3H
CC
1806
HC
C19
54M
DA
MB
415
LY2
HC
C14
19M
DA
MB
468
SU
M22
5CW
NH
CC
70H
CC
1937
BT
20H
CC
2185
HC
C11
43S
UM
185P
EZ
R75
1M
DA
MB
157
MD
AM
B43
6H
CC
3153
HC
C13
95S
UM
1315
MO
2
Trichostatin A (Histone deacetylase)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5
ERBB2AMPLuminalBasalClaudin−low
HC
C20
2B
T48
3A
U56
5H
CC
2185 LY2
SK
BR
3M
DA
MB
415
BT
474
HC
C14
28M
DA
MB
453
HC
C70
SU
M22
5CW
NT
47D
SU
M18
5PE
MC
F7
HC
C11
87H
CC
1806
HC
C14
19M
DA
MB
468
UA
CC
893
SU
M14
9PT
MD
AM
B43
6M
DA
MB
134V
IS
UM
1315
MO
2H
CC
3153
HC
C38
600M
PE
HC
C13
95B
T20
CA
MA
1M
DA
MB
157
ZR
75B
SU
M52
PE
HC
C11
43S
UM
159P
TH
CC
1954
HC
C19
37Z
R75
1B
T54
9M
DA
MB
231
MD
AM
B17
5VII
MD
AM
B36
1
Triciribine (AKT, ZNF217 amplification)
−lo
g10
GI5
0 (M
)
45
67
ERBB2AMPLuminalBasalClaudin−low
SU
M13
15M
O2
HC
C13
95H
CC
1954
MD
AM
B45
3M
DA
MB
231
SU
M52
PE
MD
AM
B36
1B
T48
3H
CC
70S
UM
185P
EA
U56
5Z
R75
BB
T54
9M
DA
MB
468
UA
CC
893
HC
C38
HC
C18
06S
UM
149P
TS
UM
159P
TM
DA
MB
157
LY2
CA
MA
1H
CC
202
MD
AM
B13
4VI
MC
F7
SK
BR
3M
DA
MB
415
HC
C11
87M
DA
MB
436
MD
AM
B17
5VII
ZR
751
BT
474
HC
C31
53U
AC
C81
2H
CC
1937
HC
C11
43H
CC
1419
HC
C14
28T
47D
600M
PE
HC
C21
85
Vinorelbine (Microtubule )
−lo
g10
GI5
0 (M
)
45
67
89 Claudin−low
ERBB2AMPLuminalBasal
HC
C11
87H
CC
202
SU
M52
PE
HC
C38
UA
CC
893
HC
C70
MD
AM
B45
3H
CC
1428
SU
M18
5PE
MD
AM
B13
4VI
UA
CC
812
SK
BR
3H
CC
2185
MD
AM
B17
5VII
BT
474
MD
AM
B36
1B
T48
3M
CF
7C
AM
A1
MD
AM
B41
560
0MP
EM
DA
MB
231
AU
565
SU
M14
9PT
ZR
75B
MD
AM
B15
7T
47D
HC
C19
54S
UM
159P
TH
CC
1143
HC
C18
06H
CC
1419 LY2
SU
M22
5CW
NB
T54
9H
CC
3153
ZR
751
SU
M13
15M
O2
HC
C19
37M
DA
MB
436
BT
20M
DA
MB
468
HC
C13
95
Vorinostat (Histone deacetylase)
−lo
g10
GI5
0 (M
)
3.5
4.0
4.5
5.0 Basal
ERBB2AMPLuminalClaudin−low
MD
AM
B46
8
HC
C38
HC
C11
87
ZR
75B
HC
C21
85
SU
M52
PE
SU
M15
9PT
MD
AM
B43
6
MD
AM
B13
4VI
HC
C11
43
AU
565
SU
M13
15M
O2
MD
AM
B36
1
SU
M18
5PE
BT
483
HC
C70
ZR
751
HC
C14
28
HC
C19
37
MC
F7
SU
M14
9PT
T47
D
MD
AM
B45
3
MD
AM
B41
5
HC
C14
19
HC
C31
53
BT
20
MD
AM
B17
5VII
CA
MA
1
BT
474
UA
CC
812
SK
BR
3
HC
C19
54
VX−680 (aurora kinase)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5
7.0
BasalClaudin−lowLuminalERBB2AMP
HC
C21
85
MC
F7
AU
565
UA
CC
812
MD
AM
B41
5
HC
C19
54
CA
MA
1
HC
C11
87
MD
AM
B13
4VI
MD
AM
B45
3
SU
M15
9PT
SU
M13
15M
O2
LY2
SU
M52
PE
MD
AM
B36
1
HC
C70
HC
C31
53
MD
AM
B46
8
HC
C18
06
ZR
751
ZR
75B
HC
C38
HC
C14
28
SU
M14
9PT
SK
BR
3
MD
AM
B43
6
MD
AM
B17
5VII
BT
474
BT
20
T47
D
BT
483
HC
C19
37
HC
C14
19
XRP44X (Ras−Net (Elk−3))
−lo
g10
GI5
0 (M
)
45
67 Luminal
ERBB2AMPBasalClaudin−low
HC
C38
HC
C11
87
MD
AM
B46
8
HC
C70
HC
C21
85
AU
565
MD
AM
B36
1
ZR
751
CA
MA
1
SU
M52
PE
MD
AM
B43
6
HC
C14
19
BT
20
HC
C19
37
HC
C14
28
ZR
75B
HC
C11
43
T47
D
UA
CC
812
SK
BR
3
MD
AM
B13
4VI
BT
483
SU
M18
5PE
SU
M13
15M
O2
HC
C31
53
HC
C19
54
MD
AM
B41
5
MD
AM
B45
3
MD
AM
B17
5VII
BT
474
SU
M14
9PT
ZM 447439 (AURKA)
−lo
g10
GI5
0 (M
)
4.0
4.5
5.0
5.5
6.0
6.5 Claudin−low
BasalLuminalERBB2AMP
