Targeting the PI3-kinase pathway in triple-negative breast cancer.
Loading...
Embargo End Date
ICR Authors
Authors
Pascual, J
Turner, NC
Turner, NC
Document Type
Journal Article
Date
2019-05-03
Date Accepted
2019-05-03
Abstract
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.
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2019, 30 (7), pp. 1051 - 1060
Source Title
Publisher
OXFORD UNIV PRESS
ISSN
0923-7534
eISSN
1569-8041
Collections
Research Team
Molecular Oncology