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Table 3 Single-node interventions which in combination with PI3K inhibitors yield an increase in Apoptosisnorm from 0.7 and/or a decrease in Proliferationnorm from 0.25

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

Perturbation Apoptosisnorm Proliferationnorm Mechanism
BCL2 = 0 1.00 0.25 Apoptosis
ER_transcription = 0 0.84 0.00 ER
ER_transcription < 2 0.84 0.13 ER
Fulvestrant = 1 0.83 0.00 ER
KMT2D = 0 0.83 0.13 ER
FOXA1 = 0 0.83 0.13 ER
BCL2_T = 0 0.81 0.25 Apoptosis
MCL1 = 0 0.75 0.25 Apoptosis
mTORC1 = 0 0.74 0.25 mTORC1
Everolimus = 1 0.73 0.25 mTORC1
cycD_CDK46 = 0 0.70 0.00 Proliferation
Palbociclib = 1 0.70 0.00 Proliferation
pRb = 0 0.70 0.00 Proliferation
E2F = 0 0.70 0.00 Proliferation
MYC = 0 0.70 0.00 ER
pRb < 2 0.70 0.13 Proliferation
cycD_CDK46 < 2 0.70 0.13 Proliferation
MYC < 2 0.70 0.13 ER
FOXO3 = 0 0.33 0.13 AKT
  1. The entries are ordered by their effect on Apoptosis. Certain node perturbations that are equivalent in the network sense and lead to the same effect are grouped, specifically: ESR1 = OFF, ER = OFF, and ER_transcription = 0; ESR1 < 2 and ER_transcription < 2; PBX1 = OFF and FOXA1 = OFF; translation = OFF, S6K=OFF, EIF4F=OFF, and mTORC1 = OFF; cyclinD = 0, CDK4/6 = OFF, and cycD_CDK4/6 = 0; cyclinD < 2, and cycD_CDK4/6 < 2; FOXO3_Ub = ON and FOXO3 = OFF