Table 1

Therapeutic agents targeting the HER2 pathway in breast cancer

Agent

Molecule

Target/mechanism

Status

Trastuzumab

Monoclonal antibody

Blocks extracellular domain of HER2

US FDA approved in metastatic and adjuvant settings [16]

Pertuzumab (2C4)

Monoclonal antibody

Blocks HER2 and HER3 dimerization

Phase III (with trastuzumab)

Trastuzumab-DM1

Antibody-drug conjugate

Binds HER2, conjugate is internalized, and DM1 toxin causes cancer cell death

Phase III

Ertumaxomab

Monoclonal antibody

Trifunctional anti-HER2 × anti-CD3 antibody

Phase II

Lapatinib

Small molecule TKI

Reversible inhibitor of EGFR and HER2 TK

FDA approved in metastatic setting [52]

Gefitinib

Small molecule TKI

Reversible inhibitor of EGFR

Phase II (discontinued because of poor results)

Erlotinib

Small molecule TKI

Reversible inhibitor of EGFR

Phase II

HKI-272

Small molecule TKI

Irreversible inhibitor of the HER-2 and EGFR TK

Phase I/II

BIBW2992

Small molecule TKI

Irreversible inhibitor of the HER-2 and EGFR TK

Phase II

Temsirolimus (CCI779)

Rapamycin analogue

mTOR inhibitor and Akt deactivation

Phase III (with letrozole)

Everolimus (RAD001)

Rapamycin analogue

mTOR inhibitor and Akt deactivation

Phase III (with paclitaxel)

Tanespimycin (17AAG)

Derivate of geldanamycin

Hsp-90 inhibitor (anti-downstream pathway element)

Phase II

Tipifarnib

Analogue of imidazole

farnesyltranstransferase inhibitor (downstream pathway element)

Phase II (with chemo and/or homonaltherapy)

GDC-0941

Small molecule

PI3K inhibitor

Phase I

EGFR, epidermal growth factor receptor; FDA, Food and Drug Administration; HER, human epidermal growth factor receptor; Hsp, heat shock protein; mTOR, mammalian target of rapamycin; TK, tyrosine kinase; TKI, tyrosine kinase inhibitor.

Morrow et al. Breast Cancer Research 2009 11:207   doi:10.1186/bcr2324