PIK3CA Mutations Drive Therapeutic Resistance in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.
Aryana R RastiAmy Guimaraes-YoungFarrah DatkoVirginia F BorgesDara L AisnerElena ShagisultanovaPublished in: JCO precision oncology (2022)
The phosphatidylinositol 3-kinase (PI3K) pathway is an intracellular pathway activated in response to progrowth signaling, such as human epidermal growth factor receptor 2 (HER2) and other kinases. Abnormal activation of PI3K has long been recognized as one of the main oncogenic drivers in breast cancer, including HER2-positive (HER2+) subtype. Somatic activating mutations in the gene encoding PI3K alpha catalytic subunit ( PIK3CA ) are present in approximately 30% of early-stage HER2+ tumors and drive therapeutic resistance to multiple HER2-targeted agents. Here, we review currently available agents targeting PI3K, discuss their potential role in HER2+ breast cancer, and provide an overview of ongoing trials of PI3K inhibitors in HER2+ disease. Additionally, we review the landscape of PIK3CA mutational testing and highlight the gaps in knowledge that could present potential barriers in the effective application of PI3K inhibitors for treatment of HER2+ breast cancer.
Keyphrases
- epidermal growth factor receptor
- tyrosine kinase
- protein kinase
- advanced non small cell lung cancer
- endothelial cells
- early stage
- positive breast cancer
- induced pluripotent stem cells
- pluripotent stem cells
- healthcare
- cancer therapy
- copy number
- signaling pathway
- dna methylation
- genome wide
- single cell
- combination therapy
- risk assessment
- gene expression
- breast cancer risk
- rectal cancer