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Efficacy of PI3K inhibitors in advanced breast cancer
Open accessAbstract
The phosphoinositide 3 (PI3)-kinase/Akt signaling pathway has always been a focus of interest in breast cancer due to its role in cell growth, cell proliferation, cell migration and deregulated apoptosis. Its activation has been linked to endocrine resistance and worse prognosis in certain subgroups of breast cancer. In addition, deregulation of the PI3K/Akt pathway including PIK3CA activating mutation is frequently present in breast cancer. Multiple efforts have been carried out to target this pathway, initially with pan-PI3K inhibitors with some hint of activity but hampered by their limiting side-effects. A recent large randomized trial in patients with endocrine-resistant PIK3CA-mutant hormone receptor (HR)-positive tumors led to the approval of the first PI3K inhibitor, alpelisib, in combination with fulvestrant. The specificity of alpelisib against the p110α catalytic isoform provided additional efficacy and a better toxicity profile. In this review, we summarize the main research with PI3K inhibitors in breast cancer and we provide some insight of potential future combinations of this treatment in breast cancer patients.
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“Unlike p110γ and p110δ, p110α is widely expressed and exclusively activated by RAS.”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [79]
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Metadata
- Authors
- Verret, B., Cortes, J., Bachelot, T., Andre, F., & Arnedos, M.
- Affiliations
- Institut Gustave Roussy (FR)
- Centre Léon Bérard (FR)
- Inserm (FR)
- Corresponding author
- Arnedos, M.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 30
- Issue
- Suppl_10
- Pages
- x12-x20
- ISSN
- 0923-7534 (ISSN-L)
- PMC
- PMC6923787
- OpenAlex
- W2996642785
- Cited by
- 221
- References
- 102
- Citations by year
- 2026: 10 · 2025: 24 · 2024: 44 · 2023: 31 · 2022: 38 · 2021: 48 · 2020: 26
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Novartis
- AstraZeneca
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Oncology › Advanced Breast Cancer Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- PI3K inhibitors, PI3K/Akt signaling, advanced breast cancer, alpelisib, PIK3CA mutation, endocrine therapy resistance, hormone receptor-positive breast cancer, fulvestrant, combination therapy, drug toxicity
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Breast Neoplasms, Female, Humans, Signal Transduction, Randomized Controlled Trials as Topic, Phosphatidylinositol 3-Kinases, Molecular Targeted Therapy
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