Format

Send to

Choose Destination
See comment in PubMed Commons below
Eur J Cancer. 2014 Mar;50(5):892-901. doi: 10.1016/j.ejca.2014.01.003. Epub 2014 Jan 22.

Resistance to human epidermal growth factor receptor type 2-targeted therapies.

Author information

1
Department of Medical Oncology, Pitié-Salpetriere Hospital, Paris, France. Electronic address: jean-christophe.thery@psl.aphp.fr.
2
Department of Medical Oncology, Pitié-Salpetriere Hospital, Paris, France.
3
Department of Oncology and Radiotherapy CRLC Val d'Aurelle, Montpellier, France.
4
Department of Oncology, Beaujon-Bichat Inter-Hospital, Clichy, France.
5
Department of Pathology, Jean Perrin Center and EA 4677 ERTICa, University of Auvergne, Clermont-Ferrand, France.

Abstract

The overexpression of the human epidermal growth factor receptor type 2 (HER-2) is an independent prognostic factor of poor outcome in patients with breast cancer. Two compounds have been registered for HER-2-positive tumour treatment: trastuzumab, a humanised antibody directed against the HER-2 extracellular domain, and lapatinib, a small molecule acting as a dual EGF-R and HER-2 tyrosine kinase inhibitor. Although both drugs improve progression-free survival, many patients' tumours will exhibit primary resistance, or develop secondary resistance, to anti-HER-2 therapies. The recent significant improvement of survival gained with pertuzumab (an antibody disrupting dimerisation of the receptor) or trastuzumab emtansine (T-DM1, a cytotoxic drug vectored by trastuzumab binding) opened the way for new registrations. This review describes the molecular mechanisms by which tumour cells may adapt to and evade HER-2 inhibition by HER-2-targeted therapies and discusses strategies to prevent and overcome resistance to trastuzumab and lapatinib. These strategies may include the establishment of predictive markers, exploration of combination therapies and modulation of nodal targets.

KEYWORDS:

Breast cancer; HER-2; Resistance

PMID:
24462377
DOI:
10.1016/j.ejca.2014.01.003
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center