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Table 2 Double-node resistance mechanisms to PI3K inhibitors ordered by their effect on Apoptosis

From: A network modeling approach to elucidate drug resistance mechanisms and predict combinatorial drug treatments in breast cancer

Perturbation 1 Perturbation 2 Apoptosisnorm Proliferationnorm Mechanism 1 Mechanism 2
MAPK = 2 MYC = 2 0.00 0.62 MAPK ER
MAPK = 2 ER_transcription = 2 0.00 0.55 MAPK ER
MAPK = 2 FOXO3 = 1, FOXO3_Ub = 0 0.00 0.50 MAPK AKT
MAPK = 1 SGK1 = 1 0.00 0.25 MAPK AKT
HER2 = 1 HER3 = 2 0.06 0.51 RTK RTK
MAPK = 1 FOXO3 = 0, FOXO3_Ub = 1 0.08 0.13 MAPK AKT
SGK1 = 1 ER_transcription = 2 0.11 0.55 AKT ER
MAPK = 1 translation = 1 0.13 0.50 MAPK mTORC1
MAPK = 1 TSC = 0 0.13 0.50 MAPK mTORC1
MAPK = 1 PRAS40 = 0 0.13 0.50 MAPK mTORC1
MAPK = 1 mTORC1 = 1 0.13 0.50 MAPK mTORC1
SGK1 = 1 MYC = 2 0.25 0.63 AKT ER
SGK1 = 1 FOXO3 = 1 0.37 0.50 AKT AKT
S6K = 1 EIF4F = 1 0.38 0.50 mTORC1 mTORC1
HER2 = 1 ER_transcription = 2 0.49 0.69 RTK ER
  1. The sustained states of the two nodes indicated in the first two columns yield a decrease in Apoptosisnorm from 0.7 and/or an increase in Proliferationnorm from 0.25 (the activities of these nodes under PI3K inhibition alone). Perturbations that involve nodes of the apoptosis or proliferation pathway are not included in this table. Certain node perturbations that are equivalent in the network sense and lead to the same effect are grouped