Growth factor receptors have long been known to drive malignant
transformation and cancer progression. The epidermal growth factor
receptor (EGFR, ErbB, HER) system is likely the best described
membrane receptor tyrosine kinase family in malignant tumors. With
implementation of the growth-inhibitory anti-HER-2 antibody
trastuzumab (Herceptin) for the treatment of HER-2-positive
advanced metastatic breast cancer, a new era has dawned in the
therapy of this malignant disease. Unfortunately,
trastuzumab-sensitive cancers invariably develop resistance to the
antibody after some time. Recent clinical studies have revealed
that these refractory tumors are still responsive to inhibition of
the HER receptor family using dual HER-1/-2 inhibitors such as
lapatinib (Tykerb/Tyverb). Moreover, a multiplicity of novel,
improved irreversibly acting small molecular HER tyrosine kinase
inhibitors are in the pipeline of many drug developing companies
and are being evaluated in the clinical setting.
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