Title : Low-scale phosphoproteome analyses identify the mTOR effector p70 S6 kinase 1 as a specific biomarker of the dual-HER1/HER2 tyrosine kinase inhibitor lapatinib (Tykerb) in human breast carcinoma cells.

Pub. Date : 2008 Jun

PMID : 18283037






4 Functional Relationships(s)
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1 Low-scale phosphoproteome analyses identify the mTOR effector p70 S6 kinase 1 as a specific biomarker of the dual-HER1/HER2 tyrosine kinase inhibitor lapatinib (Tykerb) in human breast carcinoma cells. Lapatinib mechanistic target of rapamycin kinase Homo sapiens
2 The mTOR inhibitor rapamycin was found to supraadditively increase lapatinib efficacy in MCF-7/HER2 cells [ approximately 10-fold enhancement; combination index (CI(50)) = 0.243 < 1.0 = additivity, P < 0.001] but not in p70S6K1 gene-amplified MCF-7 parental cells ( approximately 1.3-fold enhancement; CI(50) = 0.920 congruent with 1.0 = additivity). Lapatinib mechanistic target of rapamycin kinase Homo sapiens
3 CONCLUSIONS: Serine-threonine kinase p70S6K1, a marker for mTOR activity that regulates protein translation, constitutes a specific biomarker for the biological effects of the dual-HER1/HER2 inhibitor lapatinib. Lapatinib mechanistic target of rapamycin kinase Homo sapiens
4 The clinical implications of our data are that the efficacy of lapatinib might be enhanced with therapies that target the mTOR pathway. Lapatinib mechanistic target of rapamycin kinase Homo sapiens