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

Jing Liu1, Wen-Liang Kuo, Tanguy Y Seiwert

  • 1Department of Medicine, University of Chicago, Chicago, Illinois, USA.

Head & Neck
|March 26, 2011
PubMed
Abstract

Insights

Combining rapamycin and enzastaurin shows promise for treating head and neck squamous cell carcinoma (SCCHN). This combination therapy led to tumor regression in preclinical models, unlike single-agent treatments.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Rapamycin, an mTOR inhibitor, shows preclinical efficacy in head and neck squamous cell carcinoma (SCCHN).
  • mTOR inhibitors can paradoxically increase Akt activity, promoting SCCHN survival and oncogenesis.
  • Enzastaurin, an AGC kinase inhibitor, targets Akt and protein kinase C (PKC), which are implicated in SCCHN.

Purpose of the Study:

  • To evaluate the combined efficacy of rapamycin and enzastaurin in SCCHN.
  • To determine if the combination therapy is superior to monotherapy.

Main Methods:

  • In vitro studies using SCCHN cell lines.
  • In vivo studies using mice xenografted with CAL27 SCCHN cells.

Main Results:

  • Both rapamycin and enzastaurin individually inhibited targets and delayed tumor growth in mice.
  • The combination of rapamycin and enzastaurin induced significant tumor regression in CAL27 xenografts.
  • Combination therapy demonstrated inhibition of targets, survival, angiogenesis, and proliferation.

Conclusions:

  • The combination of rapamycin and enzastaurin effectively disrupts key oncogenic pathways in SCCHN.
  • This combination therapy exhibits significant efficacy in preclinical SCCHN models.

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