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Targeting the PI3K/Akt/mTOR pathway in estrogen-receptor positive HER2 negative advanced breast cancer
| Content Provider | SAGE Publishing |
|---|---|
| Author | Rusquec, Pauline Du Blonz, Cyriac Frenel, Jean Sebastien Campone, Mario |
| Copyright Year | 2020 |
| Abstract | Recently many therapeutic classes have emerged in advanced hormone receptor-positive breast cancer, which is the leading cause of cancer death in women. In absence of visceral crisis, treatment relies on endocrine therapy combined with cyclin dependent kinase 4 and 6 inhibitor. Many mechanisms lead to resistance to endocrine therapy, including the activation of intracellular signaling pathways critical for cell survival. Approximately 70% of breast tumors harbor an alteration in the phosphoinositide 3 kinase (PI3K)/Akt pathway, leading to its hyper activation. This pathway is involved in the regulation of growth, proliferation and cell survival as well as in angiogenesis and is consequently a major target in the oncogenesis. An aberrant PIK3CA mutation is a common phenomenon in breast cancer and found in approximately 40% of patients with advanced hormone receptor-positive breast cancer. For the moment, the only positive trials showing a progression free survival benefit in this population are BOLERO-2 (2012), SOLAR-1 (2019), which tested everolimus, a mammalian target of rapamycin inhibitor, and alpelisib, a PI3K inhibitor, and led to their marketing authorization. However, many other inhibitors of this pathway are promising; nevertheless their development is actually limited by toxicity, mainly cutaneous (rash), digestive (diarrhea) and endocrine (diabetes). |
| Related Links | https://journals.sagepub.com/doi/pdf/10.1177/1758835920940939?download=true |
| ISSN | 17588359 |
| Volume Number | 12 |
| Journal | Therapeutic Advances in Medical Oncology (TAM) |
| e-ISSN | 17588359 |
| DOI | 10.1177/1758835920940939 |
| Language | English |
| Publisher | Sage Publications UK |
| Publisher Date | 2020-07-28 |
| Publisher Place | London |
| Access Restriction | Open |
| Rights Holder | © The Author(s), 2020 |
| Subject Keyword | PI3K/Akt/mTOR inhibitor HR positive advanced breast cancer endocrine resistance PI3K/Akt/mTOR pathway PIK3 mutations |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology |
