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Trastuzumab: triumphs and tribulations

R Nahta1, F J Esteva

  • 1Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA. rnahta@mdanderson.org

Oncogene
|May 29, 2007
PubMed

Insights

Trastuzumab (Herceptin) targets HER2 in breast cancer, but resistance limits its effectiveness. This review explores HER2-targeted therapy mechanisms and resistance, discussing novel agents to improve outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • HER2 overexpression in 20-30% of breast cancers correlates with poor prognosis.
  • Trastuzumab (Herceptin) is a pioneering HER2-targeted monoclonal antibody therapy.
  • Trastuzumab demonstrates efficacy in early-stage and metastatic breast cancer but faces primary and acquired resistance.

Purpose of the Study:

  • To review the molecular mechanisms of trastuzumab's antineoplastic activity.
  • To discuss mechanisms contributing to trastuzumab resistance in HER2-positive breast cancer.
  • To explore novel therapeutic agents aimed at enhancing trastuzumab efficacy.

Main Methods:

  • Literature review of preclinical and clinical studies on HER2-targeted therapies.
  • Analysis of molecular mechanisms underlying trastuzumab action and resistance.
  • Discussion of emerging therapeutic strategies and agents.

Main Results:

  • Trastuzumab shows response rates of 12-34% in metastatic breast cancer (MBC).
  • Significant survival benefits are observed in adjuvant settings for early-stage HER2-overexpressing breast cancer.
  • Acquired resistance develops in most MBC patients, and primary resistance occurs in a substantial subset.

Conclusions:

  • Understanding trastuzumab's mechanisms and resistance is crucial for improving patient outcomes.
  • Novel agents hold promise for overcoming resistance and enhancing HER2-targeted therapy effectiveness.
  • Further research into combination therapies is warranted for HER2-positive breast cancer.

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