Blockade of the HER family of receptors in the treatment of HER2-positive metastatic breast cancer

Jasgit C. Sachdev, Mohammad Jahanzeb

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Breast cancer is the most common type of cancer among women and the second leading cause of cancer death in the United States. Metastatic breast cancer is considered incurable, and treatment is aimed at palliating symptoms, achieving remission, and prolonging survival. Treatment options for metastatic disease vary based on tumor surface markers and clinical factors in an individual patient and include cytotoxic chemotherapy, hormonal therapy, biological therapy, or some combination of these. An important molecular determinant of therapy is the human epidermal growth factor receptor 2 (HER2) positivity of the tumor, which affects response to HER2-targeted treatment. HER2 is a member of the human epidermal growth factor receptor family of receptor tyrosine kinases, also known as the HER family, which activates signaling that promotes tumorigenic cellular processes such as proliferation and evasion of apoptosis. Several targeted agents, including monoclonal antibodies and tyrosine kinase inhibitors that inhibit one or more HER family receptors have been developed that affect signaling through this pathway. Some of these, such as trastuzumab and lapatinib, have been approved for breast cancer treatment. Resistance to therapy is a challenge that limits the duration of benefit achieved with these agents. Therefore, combinations of HER familytargeted agents with other therapies such as cytotoxic agents, hormonal therapy, or inhibitors of other cellular pathways, are being developed to exploit synergy and overcome resistance mechanisms. Here we review the HER familytargeted agents currently approved or in development for HER2-positive metastatic breast cancer with a focus on strategies to overcome tumor resistance.

Original languageEnglish
Pages (from-to)19-29
Number of pages11
JournalClinical Breast Cancer
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2012

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Breast Neoplasms
Therapeutics
Neoplasms
human ERBB2 protein
ErbB Receptors
Biological Therapy
Cytotoxins
Receptor Protein-Tyrosine Kinases
Tumor Biomarkers
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Cause of Death
Monoclonal Antibodies
Apoptosis
Drug Therapy
Survival

Keywords

  • HER1/EGFR
  • Monoclonal antibodies
  • Resistance
  • Targeted therapy
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Blockade of the HER family of receptors in the treatment of HER2-positive metastatic breast cancer. / Sachdev, Jasgit C.; Jahanzeb, Mohammad.

In: Clinical Breast Cancer, Vol. 12, No. 1, 01.01.2012, p. 19-29.

Research output: Contribution to journalArticle

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