PIK3CA mutations in breast cancer: reconciling findings from preclinical and clinical data
Open Access
- 23 January 2014
- journal article
- review article
- Published by Springer Science and Business Media LLC in Breast Cancer Research
- Vol. 16 (1), 201
- https://doi.org/10.1186/bcr3605
Abstract
PIK3CA mutations represent one of the most common genetic aberrations in breast cancer. They have been reported to be present in over one-third of cases, with enrichment in the luminal and in human epidermal growth factor receptor 2-positive subtypes. Substantial preclinical data on the oncogenic properties of these mutations have been reported. However, whilst the preclinical data have clearly shown an association with robust activation of the pathway and resistance to common therapies used in breast cancer, the clinical data reported up to now do not support that the PIK3CA mutated genotype is associated with high levels of pathway activation or with a poor prognosis. We speculate that this may be due to the minimal use of transgenic mice models thus far. In this review, we discuss both the preclinical and clinical data associated with PIK3CA mutations and their potential implications. Prospective clinical trials stratifying by PIK3CA genotype will be necessary to determine if the mutation also predicts for increased sensitivity to agents targeting the phosphoinositide 3-kinase pathway.Keywords
This publication has 76 references indexed in Scilit:
- Comprehensive molecular portraits of human breast tumoursNature, 2012
- The landscape of cancer genes and mutational processes in breast cancerNature, 2012
- Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway–dependent and PI3K pathway–independent mechanismsNature Medicine, 2011
- Mutational characterization of individual breast tumors: TP53 and PI3K pathway genes are frequently and distinctively mutated in different subtypesBreast Cancer Research and Treatment, 2011
- Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancerBreast Cancer Research and Treatment, 2009
- Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941Cancer Cell, 2009
- Functional differences between two classes of oncogenic mutation in the PIK3CA geneBiochemical and Biophysical Research Communications, 2009
- Structural comparisons of class I phosphoinositide 3-kinasesNature Reviews Cancer, 2008
- AKT/PKB Signaling: Navigating DownstreamCell, 2007
- The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolismNature Reviews Genetics, 2006