Figure4-Source data 2 - eLife Sciences

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100. MK2206. Afatinib. Afatinib+MK2206. Drug Log [µM]. %. A. TP no rm aliz ed to. D. M. S. O. -2. -1. 0. 1. 0. 50. 100. MK2206. Afatinib. Afatinib+MK2206.
Figure 4-Source data 2

Combination therapy: EGFRi & AKTi P18T

P18T KRASG12D Afatinib MK2206 Afatinib+MK2206

50

0

-1

Drug Log [µM]

0

50

-1

Drug Log [µM]

-2

(n = 5/ 3/ 1)

0

-1

Drug Log [µM]

0

Dacomitinib MK2206 Dacomitinib+MK2206

50

0

1

1

(n = 4/ 2/ 1)

100

% ATP normalized to DMSO

% ATP normalized to DMSO

1

Dacomitinib MK2206 Dacomitinib+MK2206

-2

Afatinib MK2206 Afatinib+MK2206

50

0

-2

100

0

100

% ATP normalized to DMSO

% ATP normalized to DMSO

100

-2

(n = 7/ 3/ 2)

-1

Drug Log [µM]

0

1

(n = 4/ 2/ 1)

Combination therapy: EGFRi & PI3Ki P18T

P18T KRASG12D Dacomitinib BYL719 Dacomitinib+BYL719

50

0

100

% ATP normalized to DMSO

% ATP normalized to DMSO

100

-2

-1

Drug Log [µM]

0

50

0

1

Dacomitinib BYL719 Dacomitinib+BYL719

-2

(n = 7/ 2/ 2)

-1

Drug Log [µM]

0

1

(n = 4/ 1/ 1)

Combination therapy: EGFRi & MEKi & AKTi P18T

P18T KRASG12D Afatinib Selumetinib MK2206 Afatinib+Selumetinib+MK2206

50

0

-2

-1

Drug Log [µM]

0

1

(n = 5/ 8/ 3/ 1)

Afatinib

100

% ATP (normalized to DMSO)

% ATP (normalized to DMSO)

100

Selumetinib MK2206 Afatinib+Selumetinib+MK2206

50

0

-2

-1

Drug Log [µM]

0

1

(n = 4/ 6/ 2/ 1)

Combination therapy: MEKi & AKTi P18T

P18T KRASG12D

Selumetinib MK2206 Selumetinib+MK2206

50

0

-2

-

-1

0

-3

-2

Drug Log [µM]

-1

50

-2

-1

Drug Log [µM]

0

-2

-4

-1

0

Drug Log [µM]

Trametinib Log [µM] -3

-1 Trametinib MK2206 Trametinib+MK2206

50

0

1

1

(n = 6/ 2/ 2)

-2

100

% ATP normalized to DMSO

% ATP normalized to DMSO

0

1

Selumetinib MK2206 Selumetinib+MK2206

50

(n = 8/ 3/ 3)

Trametinib MK2206 Trametinib+MK2206

100

0

100

% ATP (normalized to DMSO)

% ATP (normalized to DMSO)

100

(n = 3/ 3/ 2)

-2

-1

Drug Log [µM]

0

1

(n = 2/ 2/ 1)

Combination therapy: MEKi & PI3Ki P18T

P18T KRASG12D

0

-2

-4

-1

Drug Log [µM]

Trametinib Log [µM] -3

0

-2

% ATP normalized to DMSO

-1 Trametinib BYL719 Trametinib+BYL719

100

50

0

-2

-1

Drug Log [µM]

0

1

0

1

(n = 3/ 2/ 2)

Selumetinib BYL719 Selumetinib+BYL719

50

(n = 8/ 2 / 2)

-2

-4

-1

0

Drug Log [µM]

Trametinib Log [µM] -3

-2

1

(n = 6/ 1/ 1)

-1 Trametinib BYL719 Trametinib+BYL719

100

% ATP normalized to DMSO

% ATP (normalized to DMSO)

50

100

% ATP (normalized to DMSO)

Selumetinib BYL719 Selumetinib+BYL719

100

50

0

-2

-1

Drug Log [µM]

0

1

(n = 2/ 1/ 1)