Lipid-conjugated telomerase template antagonists sensitize resistant HER2-positive breast cancer cells to trastuzumab

Erin M. Goldblatt, Priscilla A. Erickson, Erin R. Gentry, Sergei M. Gryaznov, Brittney Shea Herbert

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

HER2 amplification in breast cancer is associated with a more aggressive disease, greater likelihood of recurrence, and decreased survival compared to women with HER2-negative breast cancer. Trastuzumab is a monoclonal antibody that inhibits HER2 activity, making this compound an important therapeutic option for patients with HER2-positive breast cancer. However, resistance to trastuzumab develops rapidly in a large number of breast cancer patients. The objective of this study was to determine whether GRN163L, a telomerase template antagonist currently in clinical trials for cancer treatment, can augment the effects of trastuzumab in breast cancer cells with HER2 amplification. GRN163L was effective in inhibiting telomerase activity and shortening telomeres in HER2-positive breast cancer cells. We show that GRN163L acts synergistically with trastuzumab in inhibiting HER2-positive breast cancer cell growth. More importantly, we show that GRN163L can restore the sensitivity of therapeutic-resistant breast cancer cells to trastuzumab. These findings implicate that telomerase template antagonists have potential use in the treatment of cancers that have developed resistance to traditional cancer therapy.

Original languageEnglish (US)
Pages (from-to)21-32
Number of pages12
JournalBreast Cancer Research and Treatment
Volume118
Issue number1
DOIs
StatePublished - Nov 1 2009

Fingerprint

Telomerase
Breast Neoplasms
Lipids
Telomere Shortening
Therapeutics
Neoplasms
Trastuzumab
Monoclonal Antibodies
Clinical Trials
Recurrence
Survival
Growth

Keywords

  • Breast cancer
  • Combination therapy
  • GRN163L
  • HER2
  • Telomerase
  • Thio-phosphoramidates

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lipid-conjugated telomerase template antagonists sensitize resistant HER2-positive breast cancer cells to trastuzumab. / Goldblatt, Erin M.; Erickson, Priscilla A.; Gentry, Erin R.; Gryaznov, Sergei M.; Herbert, Brittney Shea.

In: Breast Cancer Research and Treatment, Vol. 118, No. 1, 01.11.2009, p. 21-32.

Research output: Contribution to journalArticle

Goldblatt, Erin M. ; Erickson, Priscilla A. ; Gentry, Erin R. ; Gryaznov, Sergei M. ; Herbert, Brittney Shea. / Lipid-conjugated telomerase template antagonists sensitize resistant HER2-positive breast cancer cells to trastuzumab. In: Breast Cancer Research and Treatment. 2009 ; Vol. 118, No. 1. pp. 21-32.
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