Abstract
Acquired hormone resistance is an old hurdle and still represents to be a constant challenge in oncology for the medical community. Most recently, mainly following the results of BOLERO-2 study, the activation of the PI3K-AKT-mTOR pathway is considered clinically relevant for tumor escape from hormone dependence in breast cancer. In the BOLERO-2 trial, a combination of everolimus, mTOR inhibitor, and exemestane significantly prolonged the median progression free survival (PFS) compared to exemestane alone in advanced breast cancer patients with acquired endocrine resistance. Therefore, the inhibitors of the PI3K-AKT-mTOR pathway are a new class of drugs in great expansion joined with great expectation. This review article focuses on this special issue and briefly reports on the results of clinical trials using PI3K-AKT-mTOR inhibitors. However, the emergence of resistance to this new class of drugs, evidenced by the basic research and the relatively less benefit shown in the clinical trials, has been emerging as a new undesirable complication. Therefore, the principal elucidated mechanisms of the resistance to the inhibitors of the PI3K-AKT-mTOR pathway and the related potential therapeutic strategies are described. A more general immunological approach to delay acquired hormone resistance has also been considered and commented upon.
Keywords: Breast cancer, acquired hormone resistance, PI3K/Akt/mTOR pathway, PI3K/mTOR inhibitors, MYC pathway, autophagy.
Current Pharmaceutical Biotechnology
Title:The PI3K-AKt-mTOR Pathway and New Tools to Prevent Acquired Hormone Resistance in Breast Cancer
Volume: 16 Issue: 9
Author(s): Andrea Nicolini, Paola Ferrari, Lucie Kotlarova, Giuseppe Rossi and Pier M. Biava
Affiliation:
Keywords: Breast cancer, acquired hormone resistance, PI3K/Akt/mTOR pathway, PI3K/mTOR inhibitors, MYC pathway, autophagy.
Abstract: Acquired hormone resistance is an old hurdle and still represents to be a constant challenge in oncology for the medical community. Most recently, mainly following the results of BOLERO-2 study, the activation of the PI3K-AKT-mTOR pathway is considered clinically relevant for tumor escape from hormone dependence in breast cancer. In the BOLERO-2 trial, a combination of everolimus, mTOR inhibitor, and exemestane significantly prolonged the median progression free survival (PFS) compared to exemestane alone in advanced breast cancer patients with acquired endocrine resistance. Therefore, the inhibitors of the PI3K-AKT-mTOR pathway are a new class of drugs in great expansion joined with great expectation. This review article focuses on this special issue and briefly reports on the results of clinical trials using PI3K-AKT-mTOR inhibitors. However, the emergence of resistance to this new class of drugs, evidenced by the basic research and the relatively less benefit shown in the clinical trials, has been emerging as a new undesirable complication. Therefore, the principal elucidated mechanisms of the resistance to the inhibitors of the PI3K-AKT-mTOR pathway and the related potential therapeutic strategies are described. A more general immunological approach to delay acquired hormone resistance has also been considered and commented upon.
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Nicolini Andrea, Ferrari Paola, Kotlarova Lucie, Rossi Giuseppe and M. Biava Pier, The PI3K-AKt-mTOR Pathway and New Tools to Prevent Acquired Hormone Resistance in Breast Cancer, Current Pharmaceutical Biotechnology 2015; 16 (9) . https://dx.doi.org/10.2174/138920101609150715141545
DOI https://dx.doi.org/10.2174/138920101609150715141545 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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