Simultaneous targeting of EGFR and mTOR inhibits the growth of colorectal carcinoma cells

Bo Li, Shuohui Gao, Feng Wei, Anita C. Bellail, Chunhai Hao, Tongjun Liu

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Epidermal growth factor receptor (EGFR) is highly expressed in colorectal carcinomas and, as a result, it leads to the activation of downstream mammalian target of rapamycin (mTOR) kinase pathways for cancer growth and progression. Clinical and preclinical studies, however, have shown that inhibition of epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) alone is not sufficient to treat colorectal carcinomas. In search of effective combination therapies, we show here that simultaneous targeting of EGFR with its inhibitor, erlotinib and mTOR with its inhibitor, rapamycin inhibits the phosphorylation and activation of downstream phosphatidylinositol 3-kinase (PI3K), Akt, mTOR and extracellular-signal-regulated kinase 1/2 (Erk1/2) pathways, resulting in the inhibition of cell cycle progression and the growth of both KRAS wild-type and mutated colorectal carcinoma cells. This study has demonstrated the principle that the combination of erlotinib and rapamycin may provide an effective therapy for colorectal carcinomas.

Original languageEnglish (US)
Pages (from-to)15-20
Number of pages6
JournalOncology reports
Volume28
Issue number1
DOIs
StatePublished - Jul 1 2012
Externally publishedYes

Keywords

  • Cell cycle
  • Colorectal carcinoma
  • Epidermal growth factor receptor
  • Mammalian target of rapamycin
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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