Current status of PI3K-mTOR inhibition in hormone-receptor positive,HER2-negative breast cancer |
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Authors: | Navid Sobhani Daniele Generali Fabrizio Zanconati Marina Bortul Bruna Scaggiante |
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Affiliation: | Navid Sobhani, Daniele Generali, Fabrizio Zanconati, Marina Bortul, Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, Trieste 34149, ItalyBruna Scaggiante, Department of Life Sciences, University of Trieste, Trieste 34127, Italy |
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Abstract: | Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and it is usually treated with anti-oestrogen drugs. However, the majority of hormone receptor positive metastatic BC patients develop resistance to anti-oestrogen treatments. The need for more down-stream therapies brought to the development of therapeutic strategies inhibiting the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) pathway. Inhibitors of the mTOR have been tested in different clinical trials; everolimus has been Food and Drug Administration approved for the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole after the encouraging results coming from BOLERO-2 trial. Similar results were obtained by the TAMRAD investigatory study testing tamoxifen in combination with everolimus in advanced BC. This editorial focuses on the results from BOLERO-2, BOLERO 4 and BOLERO-6, which tested the clinical importance of mTOR inhibition. We comment also on the role of phosphatidylinositol 3-kinase-mTOR inhibition as reported in the BELLE-2 and BELLE-3 trials and the future directions for the inhibition of this tumour metabolic axis. |
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Keywords: | Hormone receptor positive/Her2-negative breast cancer PI3K mTOR TORC1/2 Akt Everolimus |
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