HER2 as a target for breast cancer therapy.
BACKGROUND
Differential levels of HER2 expression in normal versus HER2-overexpressing breast carcinomas, together with the demonstration of a key role for HER2 in tumor progression, make HER2 an ideal target for specific therapeutic approaches.


METHODS
This review considers the clinical value of trastuzumab and lapatinib, the two HER2-targeted therapies approved for clinical practice. References were chosen by searching the PubMed and MEDLINE datasets using as search term: 'HER2', in association with 'prognosis', 'response', 'trastuzumab', 'lapatinib' and 'resistance'.


RESULTS
This review deals with HER2 as a target for breast carcinoma treatment, focusing on anti-HER2 therapies used in clinical practice, their merits and shortcomings.


CONCLUSIONS
The benefit of anti-HER2 therapies demonstrated in clinical trials indicates that HER2 is, to date, one of the most promising molecules for targeted therapy. Nevertheless, since tumor cells utilizing alternative growth signaling pathways through transmembrane receptors as well as intracellular signaling transduction molecules can bypass HER2 blockade, a future ambitious aim is the successful combination of anti-HER2 strategies with drugs directed to molecules that contribute to anti-HER2 resistance.
Tagliabue
Elda
E
Molecular Targeting Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, via G Venezian 1, 20133 Milan, Italy. elda.tagliabue@istitutotumori.mi.it
Balsari
Andrea
A
Campiglio
Manuela
M
Pupa
Serenella M
SM
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human