Insights into erlotinib action in pancreatic cancer cells using a combined experimental and mathematical approach

Table 1 Optimized parameter values for the BxPC-3 and Capan-1 model

Model parameter	Value
	BxPC-3	Capan-1
Global parameter
κ0 = EGFR phosphorylation (min-1)	0.293	0.438
κ1 = pEGFR attenuation (min-1)	0.067	0.155
κ2 = EGF-dependent ERK phosphorylation (a.u.-.1min-1)	0.388	0.482
κ3 = basal pERK dephosphorylation (min-1)	3.688	a
κ4 = EGF-dependent AKT phosphorylation (a.u.-1min-1)	0.225	0.044
κ5 = basal pAKT dephosphorylation (min-1)	0.149	a
κ6 = basal ERK phosphorylation (min-1)	0.067	0.104
κ7 = basal AKT phosphorylation (min-1)	0.013	0.007
κ8 = EGF-dependent pERK dephosphorylation (a.u.-1min-1)	4.512	8.520
κ9 = EGF-dependent pAKT dephosphorylation (a.u.-1min-1)	2.914	1.771
κ10 = pEGFR inhibition by erlotinib (μmol/L-1)	39.066	62.143
tau1 = delay for pERK (min)	29.766	66.809
tau2 = delay for pAKT (min)	3.109	13.803
Scaling parameter
erlotinib = 0 μmol/L
scale_pEGFR	0.858	0.540
scale_pERK	61.339	33.035
scale_pAKT	13.483	12.039
erlotinib = 0.11 μmol/L
scale_pEGFR	1.594	1.191
scale_pERK	27.224	29.561
scale_pAKT	8.231	8.254
erlotinib = 0.33 μmol/L
scale_pEGFR	2.522	1.955
scale_pERK	35.326	29.479
scale_pAKT	5.528	5.237
erlotinib = 1.0 μmol/L
scale_pEGFR	6.242	9.296
scale_pERK	15.631	15.464
scale_pAKT	2.569	2.340
Fixed parameter and initial condition
pEGFR (a.u.)	0	0
EGFRtot = total EGFR (a.u.)	1	1
AKTtot = total AKT protein (a.u.)	1	1
ERKtot = total ERK protein (a.u.)	1	1

a: Calculated according to Figure 1C; EGFR: Epidermal growth factor receptor; AKT: Protein kinase B; ERK: Extracellular signal-regulated kinase; EGF: Epidermal growth factor; pAKT: Phospho-AKT; pERK: Phosphomitogen-ERK; a.u.: Arbitrary units.