Targeting the PI3-kinase pathway in triple-negative breast cancer.
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Date
2019-05-03Author
Pascual, J
Turner, NC
Type
Journal Article
Metadata
Show full item recordAbstract
Triple-negative breast cancer (TNBC) is characterised by poor outcomes and a historical lack of targeted therapies. Dysregulation of signalling through the phosphoinositide 3 (PI3)-kinase and AKT signalling pathway is one of the most frequent oncogenic aberrations of TNBC. Although mutations in individual genes occur relatively rarely, combined activating mutations in PIK3CA and AKT1, with inactivating mutations in phosphatase and tensin homologue, occur in ∼25%‒30% of advanced TNBC. Recent randomised trials suggest improved progression-free survival (PFS) with AKT-inhibitors in combination with first-line chemotherapy for patients with TNBC and pathway genetic aberrations. We review the evidence for PI3K pathway activation in TNBC, and clinical trial data for PI3K, AKT and mammalian target of rapamycin inhibitors in TNBC. We discuss uncertainty over defining which cancers have pathway activation and the future overlap between immunotherapy and pathway targeting.
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Subject
Humans
Antineoplastic Combined Chemotherapy Protocols
Protein Kinase Inhibitors
Signal Transduction
Female
Randomized Controlled Trials as Topic
Clinical Trials, Phase II as Topic
Clinical Trials, Phase III as Topic
Class I Phosphatidylinositol 3-Kinases
Molecular Targeted Therapy
Triple Negative Breast Neoplasms
Research team
Molecular Oncology
Language
eng
Date accepted
2019-05-03
License start date
2019-07
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2019, 30 (7), pp. 1051 - 1060
Publisher
OXFORD UNIV PRESS