Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells

Brent N. Rexer, Siprachanh Chanthaphaychith, Kimberly Brown Dahlman, Carlos L. Arteaga

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Amplification of the HER2 oncogene occurs in approximately 25% of human breast cancers and predicts response to therapies targeting human epidermal growth factor receptor 2 (HER2), including trastuzumab, a monoclonal antibody directed against HER2, and lapatinib, a tyrosine kinase inhibitor (TKI) of HER2 and epidermal growth factor receptor (EGFR) [1,2]. HER2 is a member of the ErbB family of receptor tyrosine kinases (RTKs), which form both homo-and heterodimers, resulting in the activation of downstream signaling pathways [3]. In HER2-amplified cancers, the heterodimer of HER2 with kinase-deficient HER3 is a major activator of phosphoinositide 3-kinase (PI3K)-Akt signaling, and HER3, when phosphorylated, can directly couple to the p85 subunit of PI3K [4]. HER2amplified tumors show significant reliance on PI3K-Akt signaling [5,6].

Original languageEnglish (US)
Title of host publicationCancer Cell Signaling
Subtitle of host publicationTargeting Signaling Pathways Toward Therapeutic Approaches to Cancer
PublisherApple Academic Press
Pages55-80
Number of pages26
ISBN (Electronic)9781482299458
ISBN (Print)9781771880671
DOIs
StatePublished - Jan 1 2014

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1-Phosphatidylinositol 4-Kinase
Phosphatidylinositols
Phosphotransferases
Cells
Breast Neoplasms
Protein-Tyrosine Kinases
Receptor Protein-Tyrosine Kinases
human ERBB2 protein
Inhibition (Psychology)
Oncogenes
Epidermal Growth Factor Receptor
Amplification
Tumors
Neoplasms
Chemical activation
Monoclonal Antibodies

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Rexer, B. N., Chanthaphaychith, S., Dahlman, K. B., & Arteaga, C. L. (2014). Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells. In Cancer Cell Signaling: Targeting Signaling Pathways Toward Therapeutic Approaches to Cancer (pp. 55-80). Apple Academic Press. https://doi.org/10.1201/b17138

Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells. / Rexer, Brent N.; Chanthaphaychith, Siprachanh; Dahlman, Kimberly Brown; Arteaga, Carlos L.

Cancer Cell Signaling: Targeting Signaling Pathways Toward Therapeutic Approaches to Cancer. Apple Academic Press, 2014. p. 55-80.

Research output: Chapter in Book/Report/Conference proceedingChapter

Rexer, BN, Chanthaphaychith, S, Dahlman, KB & Arteaga, CL 2014, Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells. in Cancer Cell Signaling: Targeting Signaling Pathways Toward Therapeutic Approaches to Cancer. Apple Academic Press, pp. 55-80. https://doi.org/10.1201/b17138
Rexer BN, Chanthaphaychith S, Dahlman KB, Arteaga CL. Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells. In Cancer Cell Signaling: Targeting Signaling Pathways Toward Therapeutic Approaches to Cancer. Apple Academic Press. 2014. p. 55-80 https://doi.org/10.1201/b17138
Rexer, Brent N. ; Chanthaphaychith, Siprachanh ; Dahlman, Kimberly Brown ; Arteaga, Carlos L. / Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells. Cancer Cell Signaling: Targeting Signaling Pathways Toward Therapeutic Approaches to Cancer. Apple Academic Press, 2014. pp. 55-80
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