Molecule-targeted agents in endometrial cancer.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Delmonte
Angelo
A
Oncology Institute of Southern Switzerland, Ospedale S Giovanni, Bellinzona, Switzerland.
Sessa
Cristiana
C
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases