Gene interactions and pathways from curated databases and text-mining
Head Neck 2011, PMID: 21438065

Effect of complementary pathway blockade on efficacy of combination enzastaurin and rapamycin.

Liu, Jing; Kuo, Wen-Liang; Seiwert, Tanguy Y; Lingen, Mark; Ciaccio, Mark F; Jones, Richard B; Rosner, Marsha Rich; Cohen, Ezra Eddy Wyssam

BACKGROUND

Rapamycin is an mTOR inhibitor with preclinical efficacy in squamous cell carcinoma of the head and neck (SCCHN). However, mTOR inhibitors also increase Akt activity in SCCHN cell lines, which would promote survival and oncogenesis. Enzastaurin is an AGC kinase inhibitor with nanomolar inhibitory concentrations for Akt and protein kinase C (PKC). Moreover, Akt and PKC inhibitors have demonstrated efficacy in SCCHN.

METHODS

We hypothesized that the combination of rapamycin and enzastaurin would be more effective than either agent alone.

RESULTS

Rapamycin and enzastaurin generally inhibited putative targets in SCCHN cell lines in culture. In mice xenografted with CAL27 cells, rapamycin and enzastaurin produced growth delay. In contrast, the combination of rapamycin and enzastaurin caused regression of CAL27 tumors with evidence of inhibition of putative targets, survival, angiogenesis and proliferation.

CONCLUSIONS

These data demonstrate that the combination of rapamycin and enzastaurin disrupts critical oncogenic pathways in SCCHN and has efficacy in preclinical models.

Diseases/Pathways annotated by Medline MESH: Carcinoma, Squamous Cell, Head and Neck Neoplasms, MAP Kinase Signaling System, Neovascularization, Pathologic
Document information provided by NCBI PubMed

Text Mining Data

Akt ⊣ mTOR: " However, mTOR inhibitors also increase Akt activity in SCCHN cell lines, which would promote survival and oncogenesis "

Manually curated Databases

No curated data.