Supplement Figure.1.

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Supplement Figure.1

Supplement Figure.2 Heregulin high Heregulin low HARA A549 QG56 PC3 Patritumab 100ug/ml - + - + - + - + - + - + pERK ERK β-actin

Supplement Figure.3 B. A549 + + - - - + - + siMock siHRG Patritumab pERK ERK Heregulin A549 Patritumab - 　 + - 　 + siMock siHRG pHER3 pAKT HER3 AKT - 　 - + 　 + β-actin

Supplement Figure.4 33% inhibition Mean Pixel Density 44% inhibition

Supplement Figure.5 PC9Mock treated with erlotinib PC9HRG treated with erlotinib Ratio of expression Time (hours)

Supplement Figure.6 PC9HRG treated with erlotinib PC9HRG treated with erlotinib plus pertuzumab Ratio of expression Ratio of expression Time (hours) Time (hours)

Supplement Figure.7 PC9HRG treated with control PC9HRG treated with patritumab Ratio of expression Ratio of expression Time (hours) Time (hours) PC9HRG treated with erlotinib plus patritumab PC9HRG treated with erlotinib Ratio of expression Ratio of expression Time (hours) Time (hours)

- + Supplement Figure.8 HCC827 （EGFR mutant） Patritumab 100ug/ml pHER3 - + Patritumab 100ug/ml pHER3 HER3 pAKT AKT