Endometrial cancer is the most common gynaecological malignancy for which platinum-based and anthracycline-based combinations, with/without taxanes, are the most active but toxic treatments. The preliminary results achieved with two molecule-targeted agents suggest that a better knowledge in molecular biology of this neoplasm might improve the clinical outcome. RECENT FINDINGS: Two major types (type I and type II) of endometrial cancer are known with specific features and different changes in the genetic setting. Mutation of phosphatase and tensin homologue deleted on chromosome 10, leading to hyperactivation of the mammalian target of rapamycin pathway, is a common alteration in type I, whereas human epidermal growth factor receptor 2/neu overexpression, with increased tumour proliferation, is frequent in type II.These alterations provide the rationale for molecule-targeted treatments. Phase II studies have been performed with the three major rapamycin analogue mammalian target of rapamycin inhibitors in recurrent or advanced endometrial cancer with promising results. Hyperexpression of human epidermal growth factor receptor 2/neu in endometrial cancer justifies clinical evaluation of trastuzumab, the humanized antihuman epidermal growth factor receptor 2/neu monoclonal antibody. SUMMARY: As with other targeted therapies, antitumour activity as single agent is limited but there is clear pharmacological indication for the evaluation of combination regimens, based on preclinical and clinical data. The identification of biomarkers of biological effects might help in the selection of potential responders.

Oncology Institute of Southern Switzerland Ospedale S Giovanni Bellinzona

Molecule-targeted agents in endometrial cancer

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